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1 



PRINCIPLES OF 

THERAPEUTICS 



PRINCIPLES OF 

THERAPEUTICS 



BY 

A. MANQUAT 

NATIONAL CORRESPONDENT TO THE ACADEMIE DE ME* DICINE 



TRANSLATED BY 

M. SIMBAD GABRIEL, M. D. 




NEW YORK AND LONDON 
D. APPLETON AND COMPANY 

1910 



^v> 



. 



Copyright, 1910, by 
D. APPLET ON AND COMPANY 



Printed at the Appleton Press 
New York, U. S. A. 



CLA275473 



AUTHOR'S PREFACE 



I dedicate this book to young physicians: they will work for 
a renaissance in Therapeutics which will be the great achieve- 
ment of twentieth-century medicine. 

There is a general impression that Therapeutics is a very 
imperfect science. It would be more exact to say that it is an 
encumbered science, which is not studied with the attention it 
deserves, nor is it practised with sufficient precision. Hence, it 
often is tainted with fanciful and erroneous views. I shall be 
happy if I succeed in laying down principles to guide the young 
physician in the right direction. 

This book represents a far more considerable amount of labor 
than its size would suggest. The principles expounded herein 
are very numerous. I shall here refer only to the most important. 

I have endeavored to demonstrate that Therapeutics may be, 
and should always be, scientific, viz., an enemy to fanciful theories, 
hypothetical and hazardous deductions, and incomplete and 
superficial observations. 

I have also shown what therapeutic actions are, distinguished 
from so-called physiological actions, which are often toxic. I 
have, therefore, repeatedly combated the principle of physiolog- 
ical therapeutics, which has been a grave error. The latter often 
leads to the accumulation of medicinal and morbid poisons in 
the same organism or the same organ. 

A chapter is devoted to the differentiation of the various 
objects which a therapeutist may desire to attain. 

Another chapter is devoted to a description of the conditions 
of medicinal opportunities, including administration of medicines, 

v 



vi AUTHOR'S PREFACE 

duration of dosage, interruption, resumption, alternation, and 
fractional dosage. 

No less important is the study of the various ways in which 
harm can be done by poorly understood therapeutics. There- 
fore, serious attention is called to a multitude of errors into which 
the therapeutist may fall. 

In treating of the necessity to individualize therapeutics, I 
have indicated all the reasons which lead to variation in the 
conditions of medicinal intervention. 

In a special chapter I have discussed the considerable resources 
of non-medicinal therapeutics: hygiene, mineral waters, climato- 
therapy, psychotherapy, physical agents, and mechanical means. 

The new division of therapeutic agents which I have given will 
throw light upon the conception of a rational Therapeutics. 

Finally, I must refer to the chapter on Method in therapeutic 
studies. I do not flatter myself that I have realized more than 
an essay which, of course, needs to be perfected. 

Such being the material of the book, it might have been called 
a brief treatise on General Therapeutics; but I was afraid the 
title would then lead to the supposition that it was a speculative 
work, whereas every line of it is devoted to practice, with the 
double object of being useful and doing no harm. 



CONTENTS 



CHAPTER PAGE 

Introductory Remarks 1 

I. — Views of the Various Manners of Conceiving 

Therapeutics 12 

II. — The Forms of Therapeutic Action 25 

III. — Of the Action of Medicines 55 

IV.— Doses 76 

V. — Medicinal Opportunity 88 

VI. — Primum Non Nocere! 114 

VII. — The Elements of Therapeutic Individualization. 130 

VIII. — Influence of Environment on Therapeutic 

Results 176 

IX. — Variations of Therapeutic Activity Inherent in 

Medicines 193 

X. — Non-medicinal Therapeutic Actions 225 

XL — Method in Therapeutics 251 

XII. — Division of Therapeutic Agents 282 



PRINCIPLES OF THERAPEUTICS 



INTRODUCTORY REMARKS 

Ancient origin of therapeutics — Characteristics of its modern evolu- 
tion — Primitive and scientific periods — Intermediary phase of skepticism — 
Obstacles to the progress of therapeutics — Inadequate instruction of this 
science — Exclusiveness of the analytical mind — Influence of industries of 
medicinal products. 

It would be as unjust as untrue to believe that antiquity was 
altogether ignorant of medicine. On the contrary, therapeu- 
tists of real merit lived in all epochs. Not to speak of the 
obscure practitioners who have at all times maintained the 
prestige of the art of healing at an honorable level, the cele- 
brated names of, for instance, Hippocrates, Asclepiades, Dio- 
scorides, Galen, Fernel, Paracelsus, Glisson, Stahl, Hoffmann, 
Sydenham, Boerhaave, Haller, Cullen, Brown, Laennec, Bar- 
thez, Recamier, Bretonneau, demonstrate that patient, me- 
thodical and keen observation is apt to form physicians of 
talent, even genius. The tissue of information constituting 
our present therapeutics is made up of acquisitions accumu- 
lated by our predecessors since the origin of medicine; some 
of these acquisitions undoubtedly are more than twenty- 
three centuries old. 

There is, however, a fundamental difference between ancient 
and modern ideas: the former remained indefinitely an object 
of discussion, not infrequently of passionate controversy, for 
lack of exact demonstration, and underwent incessant changes; 

1 



2 PRINCIPLES OF THERAPEUTICS 

while the latter, scientifically established, are definitely accepted 
by all, except those conceptions which require complementary 
study. 

Whatever may be the value of the ancient physicians, such 
as those mentioned above, this value was a personal one; it 
represented chiefly an art which could not be a matter of entire 
transmission to those who followed the masters, nor be diffused 
by means of convincing reasoning. The most remarkable 
observations remained exposed to the attacks of rival schools. 
Thus, for instance, Bretonneau succeeded, by the keenest 
observation, in conceiving the idea of morbid specificity, but 
the proofs thereof so far lacked the basis of solidity that 
more than fifty years later some physicians still questioned 
it. At present, morbid specificity is no longer viewed merely 
as the result of the reflections of a genius, but as a fact 
scientifically demonstrated and so irrefutable that no man 
endowed with reason would deny it. There will be no more 
Broussais attempting to demolish the very foundations of 
medicine, because the solidity of these foundations result, in 
their main lines, from scientific certainty. 

This change has been effected in our own day. In fact, 
therapeutics has, as a science, won its place within the last 
thirty years, so that the long evolution of its history may be 
divided into two very unequal periods: one, primitive, ex- 
tending from the birth of medicine to the first third of the 
nineteenth century; 1 the other, scientific, beginning with the 

J This long period is, of course, divisible into a great number of phases 
which are not discussed in this work. Those interested in this question 
will find an extensive exposition of therapeutics in " L'Histoire des sciences 
medicales," of Ch. Daremberg, and in the article by Drs. Gilbert and Boinet, 
in the VI volume of the Traite de Pathologie generate, published under 
Professor Bouchard's direction. 



INTRODUCTORY REMARKS 3 

first studies in experimental physiology, which is now fol- 
lowing the present destinies of scientific progress. 

The primitive period is often filled with scholastic discussions, 
fanciful theories, and at times crude empiricism, but also, as 
already noted, with exact observations which have enriched 
materia medica with precious drugs, such as mercury, iron, 
opium, cinchona, digitalis, belladonna, nux vomica, colchicum, 
the best purgatives, etc., as well as with remarkable views, 
denoting at times the keenest insight, as regards the cure of 
disease by nature medicatrice (Hippocrates), spontaneous reac- 
tion of the organism (Sydenham), expectation (Stahl), irri- 
tability (Haller), morbid specificity (Bretonneau), the thera- 
peutic value of small doses (Hahnemann). 

Since the advent of the scientific period, progress is being 
made through the successive acquisition of facts as observed 
and demonstrated as rigorously as possible. Theoretic dis- 
cussions are disdained, and a larger share is given, in methods 
of research, to experimentation than to observation. Thus it 
has been possible, little by little, to substitute an increasingly 
securer stability for the oscillations of ancient medicine. 
School rivalries are restrained and, in reality, divergences 
between fair minds are less emphasized. Nevertheless, the 
beginnings of this period were welcomed with such ill grace 
that one could well describe a transitional period lasting over 
half a century, which came to an end only in recent years. 
Following, as it did, the discredit cast upon medicinal thera- 
peutics by Broussais' attacks and before the conclusive re- 
sults of the scientific method, this phase is characterized by 
skepticism in therapeutics. 

During the period of pathological anatomy, physiology and 



4 PRINCIPLES OF THERAPEUTICS 

histology held the first place in the researches of savants. The 
studies of CI. Bernard and Vulpian on pharmacodynamics 
remained in the domain of experimentation; Rabuteau did not 
go beyond the notoriety of a despised irregularity; in many 
schools the chair of therapeutics was abandoned to professors 
who did not practise medicine, or intrusted, as a debut, to 
physicians whose avowed desire was to change chairs at the 
earliest opportunity. Most of the authors of books and articles 
on pathology dismissed the question of treatment of diseases in 
a few lines, and even this much was apparently done as a con- 
cession to form. All therapeutics seemed to be reduced to the 
art of formulating, which concealed a scientific poverty explic- 
able by the inadequacy of the new medicine. 

Therapeutics had, however, long since adopted methods of 
precision. In their hospital practice and teaching Trousseau 
and Pidoux condemned to oblivion the barren theories of their 
predecessors and, benefited by the progress realized in nosol- 
ogy, they took up all the agents of materia medica in order 
to put them in contact with the diseases under observation ac- 
cording to the modern spirit, and endeavored to determine the 
service they could possibly render. In the laboratory the 
experimenters, Magendie and CI. Bernard, created pharma- 
codynamics. If medical practice has for a long time derived 
only a limited service from these advances, it is because, in 
their ignorance of pathology, phyisicans still confounded dis- 
ease and symptom and did not know how to confine the 
teachings of pharmacodynamics to the symptomatic or func- 
tional utilization of drugs, but asked of the physiological 
action of medicines the power to cure of which it was in- 
capable. Hence the discouragement of many learned phy- 



INTRODUCTORY REMARKS 5 

sicians who, on account of the imperfection of the science, 
were unable to understand the difference between physio- 
logical modification and curative action. 

It was not until the last quarter of the nineteenth century 
that the thought of curing assumed the all-important place 
in the aspirations of investigators. The greatest part of this 
evolution is to be attributed to the Pastorian School which, 
since its founder, has strived to penetrate into the mechanism 
of spontaneous recovery from infectious diseases and to study 
the remedy and the malady at the same time. To this we 
owe the birth of serumtherapy. 

Moreover, the knowledge of the procedures by which immu- 
nization and spontaneous recovery in infectious diseases are 
effected permitted distinction of the morbid cause, the evo- 
lution of the disease, the symptom and the functional dis- 
turbance, and, accordingly, institution of specific therapeu- 
tics and, at the same time, accurate limitation of the services 
to be expected of pharmacodynamics. 

Chemists also enriched therapeutics with materials of another 
class: taking as their basis certain chemical reasons of the 
action of medicaments, they created new remedies according 
to the best advantage to be derived from molecular groupings. 

Physiologists, on the other hand, having almost exhausted 
the study of principal functions, examined more profoundly 
the functions of glands and discovered a relationship between 
certain functional disorders and alteration of these glands. 
Hence the origin of opotherapy. 

Lastly, the study of physical and natural modifiers entered 
a truly scientific path and endowed therapeutics with new 
forces known under the name physiotherapy. 



6 PRINCIPLES OF THERAPEUTICS' 

While therapeutics thus received rich contributions from 
all sides, the minds also were enlarged and accustomed to 
accept truth from wherever it came. The old precept of 
Hippocrates, nihil contemnendum, dead letter until our 
day, is at last accepted by all, and we can agree, with- 
out repugnance, even with homoeopathy if we are of the 
opinion that it brings us something useful and true. 

On close view of the evolution of therapeutics as outlined 
in the foregoing pages, we find it corresponds to three well- 
characterized tendencies. During all the primitive period 
endeavor is limited to the empirical treatment of disease. 
Analytical preoccupations are necessarily restricted by lack 
of means of explanation and absence of precision in nosology. 
Individualization of prescriptions has its sole possible basis 
in the very incomplete notion of temperaments, aside from 
which everything is systematic. Thus the primitive period 
does no more than bequeath to us medicines of which our 
ancestors made an empirical and often very wrong use. As 
to the scientific period, two phases are readily recognized : 
one corresponding to the progress of experimentation and to 
the conception of physiological therapeutics; the other to 
the progress of microbiology. To the former we owe our 
knowledge of the action of medicines on the great functions, 
and our ideas on symptomatic and functional correction. 
Concurrently, clinicians, better equipped than in the past 
for observation and accustomed to greater precision, revise 
the data of empirical therapeutics. Soon, however, micro- 
biology intervenes. Research is directed to the study of the 
mysterious procedures leading to spontaneous cure of infec- 
tious diseases and to experimental realization of these pro- 



INTRODUCTORY REMARKS 7 

cedures. This latest phase, of so recent advent, has not yet 
given the full measure of its therapeutic power. Neverthe- 
less, experimental analysis of the natural evolution of infec- 
tions has already led to notable advancement, to the dis- 
covery of curative medicines (therapeutic serums), and to 
a more exact and fertile conception regarding therapeutic 
intervention, a conception which, as I shall subsequently 
show, enables us to determine the limits of the power of 
ancient medicines, more apt, most of them, to modify func- 
tions or correct symptoms than to cure disease. 

It is impossible as yet to predict the therapeutic conse- 
quences of the discoveries of bacteriology: the knowledge 
of bodies of cellular origin which intervene directly (active 
parts of vegetable juices, natural ferments of the organism), 
or which originate in the struggle of pathogenic germs with 
the organism, seems destined to extend the utilization of 
the defensive actions of the organism far beyond the limits 
of infectious diseases. 

Although the science of therapeutics is still far from perfect, 
it has in a very short time received a solid basis and a form 
which mean immense progress. Disentangled from the an- 
cient scholastic formulae, from the narrow empiricism of the 
last centuries, from the fanciful theories of our predecessors 
and the preoccupations of school, scientific analysis has elabo- 
rated precise facts in physiology, bacteriology, chemistry, 
physics, pathology, and it is already time for synthesis to unite 
these isolated acquisitions into a body constituting scientific 
therapeutics. 1 

1 We shall subsequently define what we mean by the word science, which 
is not the representation of the absolute, but is simply opposed to fancy, 
hazard, and ignorance. 



s 



PRINCIPLES OF THERAPEUTICS 



The evolution of therapeutics through the ages may, accord- 
ing to this view, be summarized in the following manner: 

Primitive Period. — Slow, irregular, and uncertain develop- 
ment of empirical therapeutics. The principal aim is treatment 
of disease. 

The advent of experimentation which 
creates pharmacodynamics and leads 
to the idea of functional and sympto- 
matic corrections. 

Revision of empirical therapeutics 
in the light of the new nosology and of 
a more rigorous observation. 



Scientific 
Period. 



Physiological 
phase 



Bacteriologic 
and 
opological phase. 



Intervention of antimicrobic proced- 
ures by which spontaneous cure of disease 
is effected. Antisepsis and asepsis. 
Serumtherapy. Opotherapy. 

Possibility of analyzing the modes of 
therapeutic action directed, as the case may 
be, to the disease, the organ or function, 
to the symptom, the lesion, or the chemical 
adulteration. 



It is to be regretted that current medical criticism does not 
fully profit by modern acquisitions. One great cause for this 
shortcoming is that instruction of therapeutics, which is the 
goal of all medicine, is not receiving adequate attention. 
Clinics are supposed to be intended particularly to promote 
instruction in therapeutics, but unfortunately the latter 
remains there as a matter of subordinate importance. I 
dare say it is taught in a defective manner, because it is one 
thing for a good clinician to have a therapeutic practice on 
his own account, however good it may be, and another thing 
to teach a science with method and complete knowledge of 
all the terms of each question. Only a specialist in thera- 
peutics, after long study and experience, can fulfil this task. 



INTRODUCTORY REMARKS 9 

An entire reorganization is to be created along these lines. 

A truly educative instruction in therapeutics supposes the 
teaching of pharmacodynamics, of therapeutics at the bedside, 
or clinical therapeutics, and of the contributions furnished by 
all the sciences (clinics, physiology, pharmacodynamics, bac- 
teriology, hygiene, climate, chemistry, physics, etc.) to the 
practice of medicine. 

Another cause of the slow progress of the science of thera- 
peutics is the essentially analytical tendency of modern medi- 
cine. Our best scientific minds are confined too narrowly 
to the observation of isolated facts, disdainful of essays of 
synthesis which they condemn systematically as "literature." 

Therapeutic science, however, which is not a specialized 
science, but thrives on contributions furnished by all sciences, 
cannot be edified in its totality otherwise than by synthesis. 
The scientific facts constitute only the material of which it 
is composed. Without these it is powerless; but neither are 
these of avail if scattered and isolated, if there be no synthetic 
mind to combine them and construct a homogeneous whole. 
To count on scientific analysis and wait until it is achieved 
in order to lay down a practical plan of treatment would 
be to ignore the fact that the fate of patients cannot be deferred. 
Any patient who appeals to the physician has a right to de- 
mand immediate treatment with the existing resources which 
reasonable deduction has established to be the best avail- 
able, in spite of uncertainties that may yet exist in their respect. 
This necessity justifies, at all epochs, the attempts of synthe- 
sis and even generalizations, hasty as they may be at times, 
but which cannot be dispensed with. 

Here, of course, is a point of weakness for scientific thera- 



10 PRINCIPLES OF THERAPEUTICS 

peutics that has been exploited by men pretending to supple- 
ment its services by their own initiative. We shall more than 
once have occasion to combat this pretention, which is by 
no means confined to some physicians but is seen among 
laymen of all classes, that one may know what one has not 
learned. If it is true that therapeutics is not yet perfect, is 
this a reason for disdaining its precise and well-established 
truths? 

Finally, the therapeutic spirit has of late years too often 
been hampered by commercial interests. New products 
and specialties, good, bad, or indifferent, are too frequently 
"pushed" into public notice. This publicity is sometimes 
founded on the exposition of serious studies (although open 
to the reproach of omitting contradictory works) ; but in most 
instances it consists, under the name of references, of a com- 
pilation without value and of appreciations and impressions 
more or less authoritative, but based upon no exact facts. 

A therapeutic observation is not the recital of recovery 
after employment of a medicine; each recital is of no value 
since it may be merely a description of the spontaneous 
evolution of the disease. In order as much as possible to 
prove the therapeutic action, an observation must be accom- 
plished by the description of symptoms; by a rigorous diag- 
nosis, supported, in case of need, by all the precision of 
the laboratory; by the diagnosis of functional disturbances 
together with a clinical description; and, in certain cases, by 
appropriate microscopical and chemical studies— conditions 
without which no observation can profitably be criticized. 
And this is not all: a therapeutic observation must include 
the probable prognosis of the morbid evolution. It is only 



INTRODUCTORY REMARKS 11 

then that one is able to form an idea, through a precise 
description of results, of the therapeutic influence of a 
treatment on the symptoms, functional disturbances, as 
well as immediate and remote prognosis of the disease. 
Even when the task is thus carefully performed, happy 
deviations attributed to therapeutic measures employed are 
so difficult to appreciate that it is necessary to verify a 
sufficiently large number of times the truth of the inter- 
pretation given in order to avoid the danger of error. 

Publicity in most cases does no more than take into ac- 
count post hoc ergo propter hoc, by which it supports the error. 

Without forgetting the precept nihil contemnendum, the 
therapeutist must distrust every medicine that has not its 
scientific warrant, every specialty that is not justified by 
sufficient reasons. 

Notwithstanding its imperfections, therapeutics has already 
become scientific, and it is therefore possible to-day to estab- 
lish its reasonable doctrine and show its consequences from 
the view-point of a good practice. This is what we shall 
endeavor to demonstrate. 



CHAPTER I 

VIEWS OF THE VARIOUS MANNERS OF CONCEIVING 

THERAPEUTICS 

Definition of therapeutics — Reasoned therapeutics — Answer to some 
objections — Empiricism and its dangers — Therapeutics of imagination — Of 
the value of instinct in therapeutics — Definition of the words: medicament, 
remedy, pharmacology, pharmacodynamics, pharmacotherapy. 

What is therapeutics? In the etymological sense of the 
word (O^paTrelv, to serve, to care), therapeutics is knowing 
how to take care of the sick. This definition, very compre- 
hensive and very correct, has one defect, however; that 
of being somewhat vague. Every author treating of ther- 
apeutics has therefore sought to give it precision according 
to his tendencies and personal opinions. Hence the con- 
siderable number of definitions proposed. 

In the first place, there has been much discussion as to 
the question whether therapeutics is a science or an art. Such 
discussions should be banished as idle and barren; they are 
of no use, as they do not succeed in convincing the contending 
parties and do not prevent the accumulation of solid infor- 
mation. If I am speaking of it, it is because the word science 
has of late been the object of widespread discussion, and 
those who deny to therapeutics the character of a science 
have asserted that, in order to treat a patient, good sense 
is sufficient, viz., some kind of divinatory instinct which they 

12 



VARIOUS MANNERS OP CONCEIVING THERAPEUTICS 13 

call art — a personal practice (how often narrow!) that has 
taught them everything. 

The fact that the laws established by scientists are neither 
absolute nor complete, and that there has been an abuse of 
insufficient knowledge by many, does not justify the excess- 
ive reaction which leads not a few to distrust the true science 
and even shun the employment of the word science for fear 
of arousing anger or laughter. For us the discussion is with- 
out interest: we are well aware that therapeutics has no claim 
for absolutism; when we say that it is a science, we take it in 
its usual sense, as it is, for instance, defined in the Diction- 
naire de Littre: ensemble, system of knowledge on a matter. 

The word science thus defined, therapeutics is a science; 
it is a science after the manner of biology of which it is a 
branch. Like biology, it adheres to the principle of deter- 
minism as this was understood by CI. Bernard; it supposes 
that the production of a phenomenon is determined by a 
condition or a set of conditions without which the phenome- 
non would not be produced and with which it is necessarily 
produced. If the determining cause, viz., the circumstance 
which determines the appearance of the phenomenon and 
constitutes its condition or one of its conditions, eludes, it is 
because we do not yet know all. When we say that thera- 
peutics is a science, we simply assert that it is composed of 
a great number of truths that are practically and humanly 
exact, and that the principle which least misleads is de- 
terminism. 

Moreover, therapeutics is a science in opposition to the 
practice of those who pretend that medicine is first of all a 
matter of good sense, of instinct, of personal observation 



14 PRINCIPLES OF THERAPEUTICS 

independent of that of others, thus justifying the criticism 
of not long ago that medicine is the only profession which 
can at times be practised by one who knows it not. 

Therapeutics is not, however, a simple and independent 
science like the various branches of mathematics, or like 
physics or chemistry; it is a composite and complex science. 
Like hygiene, it is composite, taking in, irrespective of origin, 
every useful thing it can borrow from other fields of human 
knowledge. It asserts its independence only when it comes 
to establish the biological properties of the means it makes 
use of, and especially in adapting these properties to the re- 
quirements of the diseased organism. It is more complex 
than other sciences owing to the fact that it deals with organ- 
isms complicated by malady; that is the highest degree of 
complexity which can be imagined in biology. 

Nevertheless, in order to be logical, we must say that, in 
its application, therapeutics is an art, since at this point the 
physician adds to it the value of his own personality: the 
keenness and development of his sensorial perceptions, his 
fine diagnostic penetration, his deep understanding of patho- 
logical physiology, and finally the experience acquired by 
himself. But it is a scientific art or an applied science. As 
a matter of science, therapeutics may easily be learned by 
all; as an art, it requires special education calculated to de- 
velop the aptitudes of the physician from the view-point of 
exactness in observation and reasoning. Science without art 
would be a weapon without destination; practice without 
science would be putting a dangerous weapon into the hand 
of a blind or demented person. 

In order to include both these elements I shall somewhat 



VARIOUS MANNERS OF CONCEIVING THERAPEUTICS 15 

modify the definition I have once given of therapeutics. 1 It 
is to be noted, moreover, that therapeutic science comprises 
two elements: 1. On one hand, a knowledge as exact as 
possible of all the forces which the organism can utilize in 
its struggle against a morbid state, whether they affect this 
organism itself or the cause of the disease, or produce their 
effect upon both at the same time. 2. On the other hand, a 
knowledge of the needs of the suffering organism. Scientific 
therapeutics consists in adapting the modifiers of the organism 
or of the morbid causes to the needs of the patient. 

In the present state of our knowledge, however, scientific 
therapeutics is not always realizable with absolute precision. 
In some instances the needs of the organism are not sufficiently 
understood, in others the mode of action of the measures 
opposed to the morbid state is not quite clear. It may even 
happen that we are ignorant of both the essence of the dis- 
ease and the mode of action of the remedy, as is the case when 
we deal with gout and its specific remedy, colchicum. In 
such cases the remedy which has been found serviceable by 
experience is resorted to without hesitation and without 
any foreknowledge of the morbid cause or of the mode of 
action of the therapeutic agent. For this reason a complete 
definition must take into consideration the empirical treat- 
ment of disease, acceptable when its efficacy is made cer- 
tain by a long series of favorable observations. 

Taking into account these various factors, I will define thera- 
peutics: The science of the utilizable modifiers of the organism, 

l " Therapeutics is the science from adaptation of the modifying forces of 
the organism and of the morbid causes to the fulfilment of indications 
derived from the examination of the sick and from pathogeny" (TraitS 
elementaire de therapeutique, 5th edition, 1903, Vol. I, p. 6). 



16 PRINCIPLES OF THERAPEUTICS 

of morbid causes and of diseases, and the art of applying their 
properties to the profitable correction of disturbances of health. 

This definition is as comprehensive as possible. It simply 
asks of the physician not to modify the organism without 
being well acquainted with the modifier, and to take into 
intelligent account the action exerted by it on the organism 
or on the morbid cause. This definition further admits that 
in certain cases it is permitted to act empirically upon 
disease; and it supposes that, in the application, the person- 
ality of the physician will intervene more or less successfully 
to take advantage of the sciences; but, at the same time, it 
requires that the modification of the disorders of health be 
useful and desirable. 

Is this definition satisfactory to all? We do not think so. 
Indeed, many physicians formulate objections to its principles. 

In the first place, some would like to oppose empiricism to 
scientific therapeutics. It is the place of meeting of the dis- 
appointed*, the skeptical, and those who, by an abuse of 
language, confound therapeutics with observation. 

From a triple point of view of history, method, and language, 
the word empiricism has always had two meanings : a good and 
a bad one. 

At first, empiricism (^Tretpta, experience) pretended to 
represent science through observation and experience in op- 
position to rationalism or dogmatism of the School of Alexan- 
dria addicted to theoretical discussions as early as three 
centuries before the Christian era. But precision in obser- 
vation is probably a matter of great difficulty, because, two 
centuries later, empiricism had deviated from its original 
character and the appellation implied very little respect for 



VARIOUS MANNERS OF CONCEIVING THERAPEUTICS 17 

its adherents who practised the art of healing. The same 
development has been reached in our times. After the barren 
doctrinal controversies of the end of the eighteenth and the 
beginning of the nineteenth century, Trousseau endeavored 
to rehabilitate empiricism by returning to clinical observation 
free from the theoretical confusion of his predecessors. 
But observation is of value only if exact; exact observation re- 
mained the lot of some privileged minds and the errors of 
inexact observers did not fail to give rise to bitter, at 
times scornful, criticisms against the method. 

The word empiricism thus represents two procedures: one, 
that of observation, exact at least in its intentions, is nothing 
else than the method employed in sciences, accepted by all; 
the other, that of superficial impression, insufficient or preju- 
diced observation, is an obstacle to the progress of thera- 
peutics. Hence, the former finds defenders proclaiming the 
usefulness of empiricism, while the latter brings the procedure 
into well-deserved contempt. 

But if one is obliged to establish a distinction between 
"idiotic" (Fonssagrives) and " brutal" (Stokvis) empiri- 
cism, which cannot be defended by anyone, and empiricism 
in its true sense, which consists in scrupulous observation 
and pure and simple but exact statement of facts whose 
interpretation is impossible, why should the same name any 
longer be given to two procedures of such different value? 
The defensible side of empiricism, namely, observation, is 
by no means a privilege; it is a scientific procedure common 
to all the sciences for which we claim a place among the 
methods of scientific therapeutics. 

Even with this understanding which is the most favorable, 



18 PRINCIPLES OF THERAPEUTICS 

empiricism represents but one of the means employed by 
scientific therapeutics, and this means is not the best. One 
must and often can go further. In many cases it is possible 
to reason out the intervention to be decided upon, and to 
know whether it is recovery, a functional correction, the 
soothing of a symptom, or the reparation of a derangement 
in the structure or in the chemical constitution that is to be 
expected. While we conserve for good empiricism some sort 
of admiration like that aroused at the sight of ancient 
weapons that have seen much service, we must say it is a 
method to be exceptionally employed. It easily leads to an 
exclusive symptomatic therapeutics which restricts itself 
to relieving each symptom by means of a little remedy, as 
Henle has well said; it engenders illusion, failing to distinguish 
what is due to the spontaneous development of the disease 
from that which is the result of therapeutic intervention. 
Moreover, it lacks scientific exactness inasmuch as it studies 
complex facts which seldom admit of precise conclusions. 

As to inexact empiricism, it remains the excuse of those 
who are unwilling to take the trouble to study therapeutics. 
On the pretext of personal observation and experience the 
empiricist pretends to judge everything by himself. He 
does not trouble himself about acquired knowledge. Are 
not his perspicacity and his experience sufficient to teach 
him what he does not know? He does not see that he wan- 
ders miserably all the time amid the most stupendous errors 
and the most extravagant theories. It is, therefore, neces- 
sary to distrust empiricism and hold it in the comparative 
contempt it has deserved. 

Scientific therapeutics repudiates theories of imagination 



VARIOUS MANNERS OF CONCEIVING THERAPEUTICS 19 

just as it does in exact empiricism. It is under the cover 
of so-called scientific, but in reality imaginary, theories 
that so many inventors of ephemeral remedies sell serums, 
opotherapic strange products, vegetable juices, alkaloids, 
antiseptics good for everything, depuratives, panaceas of 
all sorts which crowd therapeutics without benefit to the sick. 
The character of such products is readily known: they are 
in most instances presented as simple deductions from some 
general theoretical ideas offering no assurance of truth, and 
unable to resist the most elementary criticism. They are 
offered either without any previous study, or after a valueless 
and superficial one. 

Scientific therapeutics requires exactness in all. When it does 
not know } it is aware of it and says so; when it affirms, it proves; 
when it ventures to lay down a hypothesis, it makes reservations. 

There has in all periods of history been found another cate- 
gory of physicians who may well be classified among the 
empiricists and who pretend to see no more than the aspect 
of art in therapeutics. According to them the scientific point 
of view is useless, even harmful. They argue that each 
organism has a manner of reaction peculiar to itself — a fact 
no one denies; it is therefore impossible to know n advance 
the manner in which the one we are dealing with will react. 
What is then the use of science, result of past observation, 
which will perhaps be contradicted by the case of to-morrow? 
The latter will require the physician's intuition, instinct, 
good sense. Science is the statement of a past which proves 
nothing for the future. 

This argument is a paradox calculated to excuse ignorance 
and laziness, and to render lawful every irregularity on the 



20 PRINCIPLES OF THERAPEUTICS 

ground of individual divination to which all should willingly 
bow, whether it should come from a charlatan, an empiricist, 
or a physician in good standing. Sound minds have always 
repudiated the idea of a medical instinct capable of taking 
the place of knowledge. As Chomel wrote, as early as 1856, 
we cannot see "in the so-called occult faculty anything but 
the result of inadequate observation of facts and of a laziness 
of mind that does not care enough to scrutinize values.' ' 

It is not true that a given case cannot be judged by obser- 
vation and by the study of other cases. While it is true that 
each organism reacts in a manner peculiar to itself under the 
influence of a disturbing cause, this manner, however, belongs 
in a type that possesses a sufficient characteristic. When an 
organism is infected by a pathogenic germ, for instance, it 
reacts by a set of symptoms which occur with sufficient con- 
stancy to be recognized, in spite of individual variations, as 
those of a definite infection. Likewise, the effect of a medi- 
cine is expressed by a reaction which will almost always be 
of the same order. Individual susceptibilities capable of 
modifying this reaction are not generally difficult to foresee 
for one who makes a careful clinical study of the value and 
mode of the habitual reaction of organs. Thus we are able 
to foretell with probability, sufficient for the purposes of 
practice, the action of digitalis in plain asystole, that of mor- 
phin on pain, and that of hypnotics. We are even able to 
foretell that a certain subject will respond to morphin in a 
manner different from the one usually observed, and that a 
certain other subject will ill bear certain hypnotics. In 
specific therapeutics when we have seen twenty cases of 
malaria yield to quinin, we would know very well that the 



VARIOUS MANNERS OF CONCEIVING THERAPEUTICS 21 

same result will be obtained in the twenty-first case, so that 
when we meet with one failure (which may happen) we begin 
to doubt the exactness of the diagnosis. 

Do we not know equally well, thanks to past observation, 
that we run the risk of poisoning a patient with a certain 
dose and that we may practically be altogether safe with a 
certain other dose? Extraordinary tolerance and idiosyn- 
cratic susceptibilities do not at all invalidate the general rule. 
They do not surprise the conscientious clinician who has 
familiarized himself with the functions and habitual reactions 
of all the organs. While we have our minds open to all sorts 
of individualities, we are in possession of such probabilities 
as to the effect we are going to obtain that we practically 
go ahead with sufficient certainty. There should, therefore, 
be felt no hesitancy to utilize established ideas because of 
sophisms and paradoxes which tend to minimize their value. 
The truth is that the better we know the patient as a result 
of profound mastery of pathology, pathological physiology, 
and clinics on the one hand, and are in possession of pharma- 
codynamics and therapeutic ideas derived from precise obser- 
vations on the other, the more easily will we foresee the action 
we are to exercise upon a given patient. 

Finally, we must also refute the paradox of those who allege 
the variations of therapeutics as a reason for denying estab- 
lished results. These skeptics say, without reflection, that such 
and such a medicine has been a favorite at a certain epoch and 
thrown aside a few years later; similarly, methods of treat- 
ment once judged to be excellent have been abandoned by 
even those who had advocated them. These variations can- 
not be denied, but what do they prove? When we analyze 



22 PRINCIPLES OF THERAPEUTICS 

these variations, we see that they confirm the necessity of 
thorough therapeutic study. Some of the changes are due to 
the incessant progress of therapeutics. Take, for instance, 
a marvelous medicine for acute articular rheumatism, sali- 
cylic acid, which does not cure without some inconvenience; 
should there be any denouncing if some day it undergoes 
such a modification as to free it from its inconveniences? 
Is there any proof of error in the fact that quinin is substi- 
tuted for cinchona, mercurial injections for ingestion of pills 
or solutions, organic phosphates for mineral ones, and asepsis 
for antisepsis? Such changes are evidences of progress, not 
of therapeutic caprice. 

Other and more numerous variations are due to the fact that 
new drugs or therapeutic procedures, inadequately studied, 
come into undeserved notoriety through influential patron- 
age or shrewd advertising. A physician who is not satisfied 
with mere assertions for prescribing a medicine, but demands 
sufficient facts in order to appreciate its real value, will not 
have the embarrassment of being obliged to change his 
opinion. With a rigorous method the variations would be 
greatly lessened. 

Let us, therefore, study conscientiously and patiently the 
ideas which offer the character of certainty and take them as 
the basis of our practice. When this basis is absent, we shall 
do our best to soothe our patients, and we shall listen, with- 
out high illusions, but also without contempt, to the promises 
of empiricism, nor shall we deem it forbidden to deduce 
from what we know that which still eludes us. Thus we 
shall sometimes have the satisfaction of success and always 
that of an honest practice. 



VARIOUS MANNERS OF CONCEIVING THERAPEUTICS 23 

Scientific therapeutics has two supports: on the one hand, 
clinics and pathological physiology which enable us to 
understand the needs of the patient, and on the other, the 
remedies that are its means of action. 

The name remedy is given to all agents, no matter of what 
nature, employed for the purpose of correcting the disturbances 
of health. Remedies are very numerous. They are borrowed 
from objects of chemical study, from natural sciences, physics, 
psychology, morals, and natural media. The most imme- 
diately powerful are the medicaments. Medicaments or 
medicines are substances employed for the purpose of curing, 
aiding a cure, soothing, or concurring to the repair of a diseased 
organism. 

It is well, from the very beginning of these studies, to call 
attention to the important fact that a medicament may 
become a poison (even though it be an integral part of our 
organism) under certain conditions of dose, repetition, ad- 
ministration, or retention; such is, for instance, the case with 
chlorid of sodium. What we mean is that, under certain 
conditions, a medicinal substance is capable of causing the 
cellular elements to undergo profound modifications, so as to 
impair their vitality by chemical, physical, or even mechan- 
ical action. 

The complete study of medicaments is called pharmacology 
(<t>dpixaxov, medicament, Aoyos, study). This term is used to 
designate only the study of forms under which drugs present 
themselves, of their preparation and mode of administration. 
Of late, however, its study has also embraced pharmacody- 
namics, and all that concerns drugs: materia medica, phar- 



24 PRINCIPLES OF THERAPEUTICS 

macy, and even pharmacotherapy. This enlargement of the 
sense is against usage. 

Pharmacodynamics (or active force of medicaments) is the 
study of modifications exercised on the organism by drugs. 

Pharmacotheraphy is medicinal therapeutics. 

Therapeutics, however, makes use of many other modifiers, 
for instance hygiene, physical and natural agents, psychic 
actions, surgical actions. We propose to speak of the man- 
ner in which these various forces can, by judicious applica- 
tion, cure or palliate, or favor the reparative efforts of the 
organism. 

Such as it is, and it is very extensive, the intervention of 
the therapeutist alone would still be incomplete. In the 
etymological sense of the term, therapeutics does not only 
include prescription, it also supposes execution. Like the sur- 
geons whose organizing minds reveal themselves in all the 
details concerning environment and assistants, the physician 
must organize the minute execution of his medicinal and 
hygienic prescriptions. To this effect, it is indispensable 
to include in therapeutics the influence of the pharmacists, 
the action of nurses, and the realization of all environmental 
conditions calculated to insure for the sick the optimum of 
functioning as well as the removal of all causes capable of 
giving rise to complications or a new morbid state, or 
of hindering the effects of therapeutic intervention. The 
genius of Hippocrates could not fail to see that the patient, 
the attendants, and external things must concur with the phy- 
sician to combat the disease. The precept is forever true. 



CHAPTER II 
THE FORMS OF THERAPEUTIC ACTION 

The objects of therapeutics and the means of realizing them — Their 
division into four groups which are: 1. Therapeutics of the disease; 2. 
Organic and functional therapeutics; 3. Symptomatic therapeutics; 4. 
Reparative therapeutics — Interpretation of the terms empirical, expectant, 
naturist, pathogenic therapeutics — Is there a nosopoietic therapeutics? 

OBJECTS OF THERAPEUTICS 

The question has been raised by some whether therapeutics 
should begin with the patient or with the remedy. In reality 
the starting-point of all good therapeutics is double; it is simul- 
taneously constituted by the knowledge of the patient and 
by that of the remedy. 

The patient must be thoroughly examined by the concur- 
rence of all the senses (assisted if necessary by laboratory 
resources) in such a manner as to permit nothing to escape 
attention, from the form of fingers, the color of the skin, in- 
cluding that of the palm of the hand, and the color of ac- 
cessible mucosse to the functions of all the organs, and the 
record divided into two parts, one including everything that 
is normal and the other all that is abnormal. 

The normal features will help the therapeutist to deter- 
mine the diagnosis and prognosis, as well as the therapeutic 
aggression which can be endured by the patient. Analysis 
of the anomalies will often enable him to establish the diag- 
nosis; failing in this, it will in any case reveal the organic and 
functional deficiencies, their degree and importance; the symp- 

25 



26 PRINCIPLES OF THERAPEUTICS 

toms whose nature, intensity, and duration may be danger- 
ous and finally, in some instances, lesions or histologic altera- 
tions or chemical adulterations. Of these various elements 
some are accessible to therapeutics, others to the natural 
defenses of the organism, and still others remain beyond the 
reach of all our means of action. 

CLASSIFICATION OF THERAPEUTIC MEASURES 

The needs of the organism, having been clearly established, 
are to be met by the resources of therapeutics. These may 
be grouped into four classes as they concern the disease, the 
organs, the lesions, or the adulterations. Accordingly, there 
are four different objects and four orders of means constitut- 
ing as many different modes of treating the sick. 

I. Therapeutics of Disease. — This has been qualified 
in various ways. The most rational qualification is that 
of nosocratic (vocros, disease, KpaTtiv, to triumph) created by 
Requin 4o designate the medicaments which attack the 
cause of disease. This expression is excellent inasmuch 
as it implies no foreknowledge of the mode of action of 
remedies; it simply indicates a fact of observation, that the 
remedies cure the diseases. However, in order to express 
the most probable mode of action of this category of remedies, 
Fonssagrives has proposed the word etiocratic which specifies 
a class of medicines directed against morbid causes. 

I would prefer this expression to that of etiological thera- 
peutics which has been adopted by modern authors (Arnozan, 
Gilbert and Boinet, Roger). In fact, the word etiology 
designates all of the morbid causes and not the direct cause 
alone. Thus it is said, regarding the etiology of pneumonia, 



THE FORMS OF THERAPEUTIC ACTION 27 

that one of the causes of this disease is cold (pneumonia a 
frigore); in speaking of saturnism, the etiological influence of 
occupation and of water pipes is mentioned. Can thera- 
peutics reach these causes? If not, why speak of etiological 
therapeutics when the latter is concerned with only one of 
the morbid causes — the immediate cause, constituted by 
the pathogenic agent? If we were only sure that the so- 
called etiological medicines exerted their action on this cause, 
we would disregard the lack of precision of a word which, 
after all, would express an exact idea; but this assurance 
exists only for a few among them. 

In order not to go beyond what we know, the expression 
adopted should be confined to the fact that certain medicines 
are capable of curing certain diseases. The word nosocratic 
can therefore quite properly be applied to these medicines; 
the expression would be above criticism if there were not 
already simple expressions to designate the therapeutics 
dealing with the disease, as when we speak, in plain English, 
of therapeutics of the disease, as opposed to that dealing with 
an organ, a function, a symptom, a lesion, or a chemical adul- 
teration. 

Therapeutics of the disease is that which is concerned more 
with the disease than with the patient. It has been taught 
and repeated that there is no treatment of disease, but only 
of the sick. In its absolutism this formula is inexact; it is 
simpler and truer to say that it is necessary to individualize 
therapeutics. This is a most fundamental principle the appli- 
cations of which will be referred to in almost every page fol- 
lowing. When sulphur is prescribed for itch, quinin for 
malaria, mercury for syphilis, and antidiphtheric serum for 



28 PRINCIPLES OF THERAPEUTICS 

diphtheria, it is in reality for treating the disease; there cer- 
tainly exist, therefore, treatments of disease. But if one 
should indiscriminately apply the same treatment, that of 
itch, for instance, to adult men and to children or women 
with fine skin, or to patients suffering from grave dermitis, 
one would run the risk of provoking serious accidents in 
the latter. Individuality intervenes, therefore, in all thera- 
peutic circumstances. It intervenes in order to modify the 
choice and dose of the remedy, its repetition and mode of 
administration. 

We must conclude that there is a treatment of certain diseases, 
the number of which is quite limited. This therapeutics of 
the disease will constitute one manner of dealing with a patient. 
It is resorted to whenever it is possible to act upon the disease 
itself; we may place under it five groups of medicaments: 

1. Specific medications properly so called. 

2. Indifferent anti-infectious medicines (non-specific). 

3. Antiseptics. 

4. Antiparasitics. 

5. Antidotes or chemical neutralizers, and eliminators. 

1. The name specific is given to those treatments whose 
favorable effects are so striking, so immediate, and so constant 
as to lead to the admission of an action upon the very cause 
of the disease or the disorders constituting it. As this cause 
characterizes the morbid species, it is natural to call specific 
the therapeutic action directed against it. But we do not 
know exactly whether this action attacks the morbid cause 
directly or acts through the organism whose means of defense 
would be specifically aroused, or whether these two means are 
utilized sometimes separately and at other times concurrently < 



THE FORMS OF THERAPEUTIC ACTION 29 

Whatever the explanation may be, the striking feature in spe- 
cific treatments is the certainty of their favorable effects. 
Their application is the most successful and the easiest, but 
also the least frequent. Until a few years ago, there were 
known only three diseases with specific treatments : paludism 
and syphilis, to which may be added gout, which has a truly 
specific treatment in the use of colchicum. A similar treat- 
ment has since been discovered for acute articular rheumatism, 
diphtheria, the bite of venomous snakes, the pest; more 
recently, dysentery, sporotrichosis, trypanosomiasis. Lastly, 
the treatment of syphilis has been enriched with new specifics : 
atoxyl and arsacetin. In other diseases, the utilizable specific 
action is only preventive (tetanus) or partial (typhoid, acti- 
nomycosis), and cannot dispense with the concurrence of 
methods more general in action. Specific therapeutics has 
thus made great strides recently, and when we measure the 
advance in this direction realized in twenty years, we con- 
ceive the hope that the triumphant march forward will con- 
tinue with surer steps. 

The agents of specific therapeutics are: medicinal (mercury, 
quinin, salicylate of soda, etc.,) and biological, viz., constituted 
by the serum of immunized animals (antidiphtheric, anti- 
venomous serums). In the procedure of specific thera- 
peutics belong also vaccines or agents endowed with prevent- 
ive properties. They are of diverse origin: some are serums 
(antitetanic serum); others are bacterial products (vaccines 
of Haffkine against pest and cholera); still others are bor- 
rowed from infected animal organisms (treatment of hydro- 
phobia after a bite). 

The way of specific treatment is just open; a certain num- 



30 PRINCIPLES OF THERAPEUTICS 

ber among them are yet under study. Although all of them 
do not conform to the definition of specific medicines, bring- 
ing about recovery almost constantly, they must nevertheless 
arrest our attention as specifics, since they aim at specificity. 
Of this number are tuberculins and various serums which 
are under study for the purpose of increasing their active 
properties. 

2. Beside modes of treatment truly specific, there are others 
which resemble them by the analogy of some of their effects 
to those observed in immunization from infectious diseases. 
Their efficacy is not as decisive as that of specifics properly 
so called. They deserve, nevertheless, a place by the side of 
the latter under the title of indifferent or general anti-infectious, 
namely, without determined or differentiated action upon such 
and such an infectious germ. 

The difference between specific and indifferent anti-infec- 
tious action can be illustrated by provoked leucocytosis. When 
produced* by a microbic or toxic agent, leucocytosis is truly 
specific against this agent, but against this agent only, or nearly 
so; it will be then all-powerful. The production of leucocy- 
tosis by an agent other than the one which causes the dis- 
ease (nucleinate of soda, for example) is far less powerful 
and has a limited chance of overcoming the latter. Never- 
theless, the similarity of procedure justifies the expectation 
of some benefit which, although less certain, is not negligible. 
The procedures of indifferent anti-infectious therapeutics 
may be considered as calling into play the all-round agents 
of defense, while the specifics call out the real specialists. 

This category includes, at least provisionally, all the pro- 
cedures employed to induce leucocytosis revulsion, the em- 



THE FORMS OF THERAPEUTIC ACTION 31 

ployment of ferment metals, nucleinate of soda, injections of 
physiological salt solution, and even all the organic serums. 

3. The third group of medicines capable of combating 
disease consists of antiseptics, viz., all agents capable of 
rendering microbes harmless. 

These agents are mechanical, physical (heat), chemical 
(antiseptics properly so called), or biological. The latter 
have been included in the group of specifics on account of 
the constancy and efficacy of their action (anti-microbic 
serums). 

Chemical antiseptics, which alone are usually designated 
under the name antiseptics, are subject to a remark that 
should always be remembered: if these substances exert a de- 
structive action upon microbes they generally exert at the same 
time a destructive action upon the anatomical elements with 
which they come in contact, a fact which limits their value from 
the view-point of local antisepsis. Similarly, true antiseptics 
have all proved to be energetic poisons. This fact prevents 
any intensive internal antisepsis, because, in order to realize 
it, one would be compelled to impregnate the whole organism 
with a toxic agent beyond the resisting power of the vitality 
of living matter. For this reason internal antiseptics have 
no chance of success except when they are specific, that is 
to say, when the pathogenic germ upon which they act is so 
very sensitive to their influence that it is affected by them, 
while the elements of the organism are not to any important 
extent affected. As to non-specific antisepsis, which I have 
called indifferent (not differentiated with regard to such and 
such a micro-organism), we must not count upon a very 
energetic action with the medicaments so far at our disposal. 



32 PRINCIPLES OF THERAPEUTICS 

Antisepsis is energetically exercised on objects and resisting 
surfaces such as the skin; elsewhere its use is quite limited, 
though by no means unimportant. 

4. Antiparasitics act in two ways: Some kill the patho- 
genic parasites (parasiticides); others paralyze or modify 
them in some measure and thus facilitate their expulsion 
(parasitifuges). 

5. Antidotes is the name designating generally all sub- 
stances which inhibit the action of poisons either by forming 
with them inoffensive compounds (chemical, true antidotes, 
counterpoisons), or by producing opposite physiological effects 
(physiological antidotism). Authors are not agreed, how- 
ever, as to the meaning appropriately to be attributed to the 
word antidote, which is reserved by many for chemical 
neutralizers. In view of the idea of nosocratic therapeutics, 
this distinction imposes itself, since chemical antidotism is 
alone worthy of the name nosocratic. Physiological antidot- 
ism is directed to the patient, to his organs and functions 
rather than to the poison itself. Antagonism is then appealed 
to, and preferably apparent antagonism which is essentially 
functional. We shall subsequently see that physiological 
antidotism, or antagonism, is limited by several conditions, 
and especially by the degree of the intensity of the action 
exerted by the poisons upon the anatomical elements. When 
the latter are deeply affected, physiological antidotism is 
necessarily powerless 

The eliminators of microbic products or organic poisons 
resulting from autointoxication constitute the agents directed 
against the toxic substances as well as, in some . measure, 
against the disease. If they do not constitute nosocratic 



THE FORMS OF THERAPEUTIC ACTION 33 

agents, they are nevertheless necessarily indicated to justify 
in some measure then- systematic employment in the treat- 
ment of disease giving rise to intoxication. The system must, 
however, be adapted to the patient's needs and organs in 
accordance with the principle of therapeutic individualization. 

In this category belong water diet and cold bathing in 
typhoid fever, which procedures act particularly as elimi- 
nators of soluble diffusible toxins. Here also belong bleeding 
and diuretics in uremia. This mode of intervention is limited 
by the nature and properties of toxins, not all of which are 
apt to be eliminated. The most redoubtable among them 
acting after the manner of ferments and being inaccessible to 
eliminators. 

It is well to note that these therapeutic measures belong, 
in a certain degree, to the group of functional stimulants, 
which they touch on the one hand, and reparative thera- 
peutics on the other. 

In spite of the wide range which therapeutics of the disease 
thus covers, it still leaves out of its action a very great number 
of morbid states for which a far more difficult and complicated 
therapeutics, requiring the combined efforts of clinics and 
pharmacodynamics, must intervene; that is, the one which 
is to be directed against organic disturbances, functional 
disorders, or symptoms. The disease, however, will not 
be directly influenced thereby, but will continue its evolution 
in spite of intervention; but its prognosis will be improved, 
at times considerably, through the favorable organic and 
functional corrections which enable the organism to enjoy its 
maximum of resistance and defense. Hence, there are two 
other modes of therapeutic action: one of these I will call 
3 



34 PRINCIPLES OF THERAPEUTICS 

organic and functional therapeutics; the other, symptomatic 
therapeutics. 

II. Organic and Functional Therapeutics. — Organic and 
functional therapeutics is the one which strives to correct, 
through action upon one or several organs, functional disorders 
dangerous by reason of their intensity, importance, or dura- 
tion, in the course of the evolution of a morbid state. This 
definition implies that functional disturbances may be negli- 
gible if they be neither very marked, nor important, nor 
persistent, or if they occur in a state of health under transi- 
tory influences. Such are often the vomiting of pregnancy, 
palpitations, and arythmia caused by some nervous distur- 
bance, etc. 

The therapeutics which I call functional is often designated 
under the names physiological or pathogenetic. But the 
former (physiological) has had in therapeutics various mean- 
ings (Broussais' physiological doctrine, physiologic thera- 
peutics of Rabuteau, that of G. Sec going so far as to deny 
morbid specificity) which it would be well to abandon. Patho- 
genetic therapeutics designates not only the one that "derives 
its inspiration from the mode of action of causes," as Roger 
assumes, but also the other which "attacks the cause of the 
disease/ ' as Bouchard defines it. Pathogenetic therapeutics, 
thus including that which is directed against morbid causes 
and that which derives its inspiration from the mechanism 
of functional troubles, would be too broad and not sufficiently 
precise; it would comprise nosocratic therapeutics as well as 
functional therapeutics whose procedures differ too greatly 
not to be distinguished. Moreover, this classification has 
often the serious inconvenience of being impossible by reason 



THE FORMS OF THERAPEUTIC ACTION 35 

of our ignorance of the mode of production of morbid 
disturbances. 

Functional therapeutics is the method most frequently 
resorted to. It intervenes sometimes through direct action 
upon the suffering organs upon which the disturbed functions 
depend; it strives thereby to render their function more regu- 
lar or more effective or more responsive to the necessities of 
the moment. Renal diuretics act thus upon the kidneys, and 
some toni-cardiacs upon the heart. This direct action is 
always a matter of delicate management, because organs 
suffering from some intoxication or lesion cannot always be 
subjected with impunity to energetic action. This is the reason 
that the practitioner is especially cautioned against digitalis 
and large doses of caffein when the vitality of the myocar- 
dium is lowered by some toxic influence, and against diu- 
retics liable to irritate the renal epithelium in epithelial neph- 
rites. For the same reason also it is advisable, whenever 
possible, to seek correction of functional disturbances due to 
some profound alteration of an organ, through some in- 
direct procedure, or some action upon the nervous system 
of the diseased organ. Thus, for instance, spartein is pref- 
erable to digitalis when the heart is involved in the course 
of an infectious disease, because the former exerts on the 
heart an indirect dynamogenic action, of bulbo-myelitic 
origin, and seems not to affect in any manner the myocardiac 
contractility. At times, however, it is possible to utilize 
concurrently both procedures, direct and indirect; to asso- 
ciate, for instance, theobromin and a diet of dechlora- 
tion in Bright's disease complicated with retention of the 
salt. 



36 PRINCIPLES OF THERAPEUTICS 

Organic therapeutics usually seeks to modify the organs 
because of necessary functional corrections, since organic 
anomaly demands no intervention except when attended 
by functional disorder. Thus an organic lesion of the heart 
well compensated or well tolerated, viz., with adequate func- 
tioning of the organ, needs no more than hygienic care for 
the purpose of maintaining this state as long as possible. 
Therapeutics properly so called is called for only when the 
function declines. 

Moreover, fundamental functional disturbances should be 
distinguished from those which are accessory; irregularity or 
rapidity of cardiac contractions, for instance, may co-exist 
with a sufficient circulatory impulsion. In such cases there is 
generally no occasion for intervention. A functional anomaly, 
however, even when the state of health is apparently good, 
must always inspire reservation. Thus oliguria has sometimes 
been noted in persons, especially women, enjoying for a long 
period apparently perfect health. Such a state should always 
arouse suspicion, for I have seen precocious arterial accidents 
in persons presenting this anomaly. It seems to me that, 
even in the absence of morbid disturbances, the diuresis of 
oliguric subjects should be increased, and that the causes of 
persistent cardiac irregularity and acceleration should be 
looked for and removed, if possible, by hygienic treatment. 
These cases, in fact, do not seem to me to require medicinal 
therapeutics, whose action cannot be sufficiently prolonged 
without inconvenience. 

Practically, organic therapeutics and functional therapeu- 
tics are confounded since they are carried out through the 
same measures. But these measures are not of the same 



THE FORMS OF THERAPEUTIC ACTION 37 

value: the function may be modified by the application of 
indirect measures, as has already been stated, without the 
diseased organ being affected. The heart may be stimulated 
through its nervous system without the myocardium being 
acted upon. Respiration may be facilitated, according to the 
cause of dyspnea, by stimulation of the respiratory center, 
by strengthening the heart's action, by increasing diuresis, 
or by preventing the production of autointoxication through 
alimentation. Likewise, diuresis may be favored without 
diuretics, by cold bathing, by a water diet, perhaps by means 
of certain postures, etc. It is necessary to establish all these 
distinctions in order to proportion the effort of an organ to 
its strength, and obtain the maximum of functional correction 
without overtaxing the organ. 

Functional therapeutics is utilizable also for the purpose 
of supplying the functions of certain fluids. But here func- 
tional action approaches etiocratic action. It is even some- 
times identified with defense of the organism, and it is very 
likely that, in the near future, the group which we shall now 
consider will be more regularly placed among the agents of 
nosocratic therapeutics. 

Perhaps every cell of the organism, and most assuredly 
certain special glandular cells (cells of the thyroid, suprarenal 
capsules, testicles and ovaries, liver and thymus) have the 
property of secreting active products which play a large physi- 
ological part. Therapeutics has endeavored for the last fif- 
teen years to take advantage of this fact by the administra- 
tion of extracts of organs and of tissues which are supposed 
to contain those products. This method of treatment was 
christened by Landouzy opotherapy (ottos, juice). 



38 PRINCIPLES OF THERAPEUTICS 

Opotherapy is yet far from being well studied. All we 
have asked of it so far is to replace absent or insufficient 
internal secretions, by organic substances serving the same 
purpose, but without knowing exactly the object to be attained 
nor even being sure by precisely what substance we are acting. 

The action of total organic juices offers rather functional 
properties. The best known of these properties seem to be 
to stimulate the organs which produce them to secrete more 
actively these same products on the one hand, and, on the 
other, to exert very intense action upon nutrition (thyroid 
gland) and circulation (suprarenal capsules, thyroid). 

Opotherapy seems to be destined to occupy in the future 
the first place in therapeutics by supplying the organism 
with resisting and defensive measures through the body fluids 
which are sometimes deficient. The present insufficiency of 
the method is due to various reasons: first, its recent crea- 
tion, the difficulty of securing active preparations, and, 
lastly, the slight value of many of the clinical observations 
serving as the basis of the method. 

Recently, however, Dr. Choay has shown (Societe de thera- 
peutique, June 24, 1908) that concentration of the pulp of 
organs in vacuo and in the cold, furnished extracts equivalent 
to the pulp. On the other hand, the chloroformic dialysis 
of Drs. Dastre and Permilleux gives an hepatic juice of great 
activity. Such procedures may enable the investigators to 
avoid spoiling the properties of the organs which so easily 
results from the action of physical and chemical agents. Nu- 
merous are the studies recently undertaken to determine 
the constituents of organic juices (nucleo-proteids, albumens, 
globulins, lipoids). These researches promise to be fruitful. 



THE FORMS OF THERAPEUTIC ACTION 39 

Great, therefore, are the possibilities of opotherapy as re- 
gards the resistant and defensive functions of the organism. 
While hoping to see the realization of this, we shall continue 
to consider opotherapy as an agent of functional therapeutics. 

By the side of suppliers will soon probably be placed a class 
of analogous remedies which might be designated 'protectors. 
I would apply this title to substances which, like cholesterin, 
are capable of effectively antagonizing the destructive action 
of certain cytotoxins or substances favorable to the action of 
these cytotoxins. Thus cholesterin, which I take as an illus- 
tration, is antihemolytic in regard to a certain number of toxic 
serums (Iskovesco), in regard to the hemolysin of cobra's 
venom (Kyes, Minz), and to saponin (Ramson). Its pro- 
tective action is mostly exercised through the destructive 
power it exerts upon these hemolytic poisons. Iskovesco's 
therapeutic researches on anemic conditions strengthen the 
hopes aroused by laboratory studies. 

This protective action of cholesterin is exercised not only 
upon poisons of animal origin, but also upon microbic toxins. 
Thus Vincent has demonstrated that this substance possesses 
the power to destroy the poison of tetanus. Gerard and 
Lemoine (of Lille) have even affirmed that it arrests the 
progress of tubercular lesions. 

It is yet too early to conjecture the future role of suppliers 
and of protectors in therapeutics. We hope it will be consider- 
able, in view of the spontaneous recoveries that are doubtless 
favored, at least in part, by certain conditions of the body fluids 
which we shall probably succeed some day in realizing at will. 

III. Symptomatic Therapeutics. — In a very considerable 
number of cases, by restoring disturbed functions as nearly as 



40 PRINCIPLES OF THERAPEUTICS 

possible to a normal state, we correct the symptoms through 
which their disturbance was expressed. The reverse is true 
only in rare instances; one may attenuate or remove a symp- 
tom without modifying the corresponding disturbed func- 
tion. Thus, the symptom dyspnoea may easily be modified 
in an asystolic patient by reinforcing the cardio-renal functions 
by means of digitalis; this is an illustration of functional 
therapeutics. But if I should confine my effort to improving 
only the dyspnceic condition by means of heroin, for example, 
the functional disorders of asystole would persist as before. 
The same is true of the insomnia in cardiac affections which is 
palliated by the functional treatment of asystole, but whose 
attenuation by means of some hypnotic would not be followed 
by any marked effect upon the heart's action. 

Functional treatment should precede symptomatic treatment 
whenever the symptom depends upon a known functional 
disturbance which it is possible to correct. Very often, how- 
ever, the pathogeny of the symptom is unknown, or if it is 
known, remains inaccessible to rational therapeutics; such is, 
for instance, fever in many infections. Pure symptomatic 
treatment is then the only one to consider. 

The therapeutics of a symptom taken by itself, viz., regard- 
less of its pathogeny, should never be practised except when 
nothing better can be done. At any rate, there is no advan- 
tage in combating a symptom unless it be dangerous of itself 
(certain hemorrhages related to an organic state), too painful to 
bear (pain, dyspnoea), too persistent (prolonged fever), or when 
it exerts an unfavorable influence upon the concomitant mor- 
bid state (pain, insomnia, fever) or upon a function. Even 
then, in order to attack it, one should make use of recognized 



THE FORMS OF THERAPEUTIC ACTION 41 

harmless measures. In all other cases symptomatic treat- 
ment, on account of its dangers, should be resorted to only 
with reservation. 

The danger of symptomatic treatment may result either 
directly from a harmful action of the medicine (antipyrin, 
chloralose), from possible habituation (morphin, heroin, 
cocain, chloral), from ignorance of the effect produced upon 
the evolution of the disease by suppression of a symptom 
whose meaning is not always understood (fever for instance), 
or from deceptive security inspired by suppression of a symp- 
tom capable of serving as a guide in decisions to be taken 
(suppression of pain by morphin in appendicitis). The dan- 
ger may result from secondary detrimental effects, such as 
oliguria caused by morphin, antipyrin, vesicatories, and 
depression following the stimulant action of caffein. Lastly, 
an aggravation of the morbid state which has engendered 
the symptom may result as a consequence of neglecting bet- 
ter therapeutics (aggravation of tubercular evolution in spite 
of diminished coughing). At any rate, symptomatic thera- 
peutics does not generally afford more than momentary 
relief. 

However limited the services rendered by the correction 
of symptoms may be, they are nevertheless precious in certain 
cases. It is to them that we owe our power to soothe incur- 
able patients, to enable patients to pass difficult moments 
without suffering (postoperative period), and even to exer- 
cise a favorable influence upon the general conditions of pa- 
tients and upon certain functions. Thus, for example, the 
diminution of temperature obtained by means of cryogenin 
in some highly toxic tuberculoses renders rest and alimenta- 



42 PRINCIPLES OF THERAPEUTICS 

tion possible, which would be missed if the high temperature 
was allowed to persist. In the same manner the seda- 
tion of the fatiguing cough of certain tuberculous patients 
may improve their general state by preventing vomiting. A 
hypnotic appropriately prescribed will spare neurasthenics 
a series of long sleepless nights which would increase the 
exhaustion of their nervous systems. In some cases it may 
happen that correction of a symptom is followed by improve- 
ment of disturbed function due to the very existence of this 
symptom. The spasms caused by pain cease or diminish 
with the soothing of the pain, as is often seen; insomnia 
caused by pain naturally disappears when the pain in ques- 
tion has disappeared; the digestive function is improved by 
diminution of temperature in feverish tubercular subjects. 
IV. — Reparative Therapeutics. — Examination of the 
patient has thus furnished three important indications to 
fulfil: to reduce the specific cause, to correct the organic 
and functional disorders, to repress the symptoms that are 
dangerous in themselves. It imposes a fourth indication with 
reference to the reparation of structural lesions and chemical 
alterations, and even the correction of disturbances due to 
some defective cellular dynamism. It is to its realization 
that I will apply the name reparative therapeutics. We 
sometimes deal with a lesion accessible to direct action. 
Then surgical therapeutics especially intervenes to modify 
or exclude the lesion. In other cases the favorable modi- 
fications may be obtained by employing very simple agents 
such as emollients, astringents, and weak antiseptics. The 
modifiying agent is not necessarily medicamental ; ulcer of 
the stomach, inflammations of the digestive tract and its 



THE FORMS OF THERAPEUTIC ACTION 43 

adnexa require above all else an appropriate diet, while drugs 
are of secondary importance. In other cases the lesion is 
inaccessible to direct action, but it is modifiable through 
the intervention of medicines some of which act specifically 
(mercury), some by functional action (iodin), others by a 
more obscure process (arsenic), and still others indirectly 
through the reparation of alterations in the general system, 
as in the case of local tuberculoses. 

Reparative therapeutics also intervenes to correct defi- 
ciencies in the mass of the organism (fattening diet, cod- 
liver oil, etc.), in its chemical constitution (phosphorus), or 
in the composition of the blood (iron). 

This reparative therapeutics is also resorted to for correct- 
ing chemical adulterations induced by insufficient exchanges. 
It succeeds sometimes by elimination (diaphoretics, diuretics, 
purgatives, water diet), at other times by stimulating the 
nutritional activities (alkalines, hygiene, climate), or else by 
combining these too procedures (general massage, alkaline 
mineral waters). Finally, the correction of nervous devia- 
tions by psychotherapy and suggestion is also a mode of re- 
parative therapeutics. Correction of the body fluids, such as 
viscosity of the blood whose importance is just being appreciated, 
comes also within the sphere of reparative therapeutics (ali- 
mentary hygiene, iodids). 

In practice these four therapeutic procedures (specific, 
organic and functional, symptomatic, reparative) may con- 
currently intervene and accord each other mutual support. 
They sometimes even overlap one another, so vague are their 
limits, and it is by analysis that each receives credit for what 
belongs to it. Thus at times hemostasis is referred to as an 



44 PRINCIPLES OF THERAPEUTICS 

example of symptomatic therapeutics. Hemorrhage is, in 
fact, a symptom, and one practises symptomatic therapeutics 
in arresting it by means of direct coagulating action on the 
seat of the hemorrhage (coagulating influence of iron chlorid, 
for instance, justly abandoned to-day), or by ligature of the 
artery. But that is an exception. In most cases some 
functional action such as the contraction of capillaries by 
ergot or through the action of cold is resorted to. It is also 
possible to act by lowering the blood pressure (ipecacuanha, 
amyl nitrite). Hemostasis is then no longer symptomatic, 
since it is brought about by functional modifiers. If the case 
be one of traumatic hemorrhage, ligature of an artery is a re- 
parative procedure, or even more rigorously etiocratic rather 
than a symptomatic procedure. 

In other instances analysis is still more delicate. Leuco- 
therapy, for example, is a transition between specific thera- 
peutics which it approaches by its means and its end, and 
functional therapeutics wherein it is included because it stimu- 
lates a normal function. Eliminators are alike elements 
of nosocratic, functional, and reparative therapeutics. They 
might properly be studied under any of these three methods. 

The same therapeutic agent may be useful in several ways. 
Thus cold bathing in typhoid fever acts as a functional remedy 
in favoring diuresis, as a reparative agent in promoting de- 
puration of the organism, and as a symptomatic in lowering 
the temperature. Mercury, in the case of a syphilitic lesion, 
acts at the same time as a specific and a reparative; it is 
nothing else than a specific when employed as a preventive. 
It has already been noted that many of the agents combat 
symptoms by means of some functional modification. Diet 



THE FORMS OF THERAPEUTIC ACTION 45 

first modifies the function, secondarily the symptom, then the 
organ, and finally the organism. 

It is very essential in practice to thoroughly comprehend 
what is to be accomplished. The interpretation of influences 
exerted is by no means idle speculation; it alone enables us to 
be precise and to proportion the means to the requirements 
of each case; it alone emancipates us from the yoke of empiri- 
cism which is an inferior and blind procedure; lastly, it alone 
permits the realization, as far as possible, of the principle which 
I ask permission to quote from my Traite elementaire de 
Therapeutique, according to which a "therapeutic intervention 
must be commanded by a necessity of morbid origin and be 
carried out through measures scientifically known." 1 

Specific treatments are undoubtedly becoming more and 
more predominant in therapeutics. It is by no means useless 
to emphasize this point because there has long been a mis- 
understanding as to the mode of action of medicaments. The 
minds were so overwhelmed with the importance of patho- 
logical anatomy that they were too exclusively concerned 
with lesions and disturbances dependent thereon. On the 
other hand, they desired to see in therapeutic actions only 
physiological actions. It is to-day known that specific effects 
are independent of appreciable physiological effects, and that 
intoxications are worse than lesions, a fact which diminishes 
the importance of functional therapeutics especially in infec- 
tious diseases. 

Anyone who has struggled against death, during the last 
phases of life, must have noted the inadequacy of physio- 

1 In my "Traite de Therapeutique," written eighteen years ago, I was 
perhaps still too much imbued with the lessons of the physiological school, 
" physiologically known." 



46 PRINCIPLES OF THERAPEUTICS 

logical modifiers in too many instances. If, in accordance 
with the long predominant idea that an anatomical lesion or 
a functional disorder is necessary to end life, one directs all 
efforts toward the maintenance of functional regularities, one 
often sees his patient succumb in spite of apparent success, 
at a moment when the heart is still sufficiently strong to per- 
form its function and when no lesion exists in the organism 
capable of causing death. But some intellectual obscurity 
is observed. At the same time the skin becomes pale and 
livid; a few drops of sweat appear on the face; the eyes, 
sunken, assume a glassy aspect. There is therefore a pro- 
found disturbance in the exchanges and consequently an 
alteration in the cellular elements and in the fluids, while the 
heart is still acting with energy sufficient to prolong life for 
several hours. But death has already done its work by strik- 
ing the cellular elements and has, in reality, preceded the last 
breath and pulsation of the heart. 

Functional therapeutics has, therefore, its limitations. At 
the same time that we think of the heart, lungs, kidneys, liver, 
and the nervous system, we must be mindful of infectious and 
intoxicating processes and strive to check them through 
specific procedures, or, in their absence, by measures as closely 
approaching them as possible and likely to develop the habit- 
ual modes of self-defense of the organism, namely, the play 
of emunctories (diuretics and laxatives), leucocytic multi- 
plication, perhaps the mobilization of an important mass of 
leucocytes (abscesses purposely created, setons), stimulation 
of exchanges, renewing of adulterated media (blood-letting), 
and sometimes cellular reactions (injections of physiological 
salt solution). There will be failure in presence of certain 



THE FORMS OF THERAPEUTIC ACTION 47 

inertias or irremediable exhaustions, as in the case of the very 
aged, or in that of secondary infections which find a soil pre- 
pared particularly for their destructive activity, as if they 
were favored by a real anaphylaxis, or when the toxic princi- 
ples behave as though they were natural ferments or as if 
they adhered too closely to the cellular elements to be diffused 
and eliminated. 

Later on, therapeutics will find better weapons against mar- 
asmus and cachectic states, not, however, in medicaments (as a 
specific should be necessary, and the number of such is quite 
limited), but in the glands, tissues, and body fluids of animals. 
Let us always keep in mind that a young and untainted sub- 
ject offers the greatest chances of recovering spontaneously from 
curable infectious diseases. He, therefore, possesses within him- 
self the cellular or fluid elements of recovery. It is because 
of the absence or insufficiency of these elements that the aged 
and the cachectic cannot recover. It is conceivable that cer- 
tain medicines should be capable of actively stimulating such 
elements, but none is known capable of creating them. It 
remains for future efforts to discover these curative elements, 
to extract them from the bodies of animals and infuse them 
into patients needing them. 

If specific therapeutics has a predominant importance in 
the treatment of acute illness, reparative therapeutics holds 
the first place in that of chronic maladies. Symptomatic 
therapeutics is too often the ultimate resource in incurable 
diseases. 



48 PRINCIPLES OF THERAPEUTICS 



EMPIRICAL, EXPECTANT, NATURISTIC AND PATHOLOG- 
ICAL THERAPEUTICS 

We have not admitted the expressions of pathogenetic, 
empirical, expectant, naturistic therapeutics. We have already 
explained the value of the term pathogenetic. In fact, em- 
piricism, as it is ordinarily understood, enjoys little credit 
(see page 16). I do not mean to say that no medicine should 
ever be employed whose action is not strictly known; but any 
medicine whose action is unknown or obscure, but which is 
nevertheless prescribed on the ground of some real or hypo- 
thetical virtue, should at least provisionally enter into one of 
the four categories we have established. 

Pure expectation does not exist and has perhaps never existed; 
scientific expectation is a mode of reparative therapeutics 
which puts the organism at its optimum of functional activity 
and of natural defense. This is therapeutics of the master, 
expert in prognosis as well as in diagnosis, in pathological 
physiology as well as in physiology and hygiene. Expecta- 
tion pure and simple would be inexcusable negligence. 

Naturistic therapeutics consists in exaggerating the func- 
tional disturbances which are supposed to be useful for recovery. 
To purge in diarrhea, to constipate a patient suffering from 
peritonitis, to cauterize an atonic wound would be applica- 
tions of this form of therapeutics. I do not see how so diverse 
procedures can logically be brought together to form a group. 
When a patient suffering from diarrhea is purged, it is to favor 
the eliminating effort of the intestines; it constitutes, there- 



THE FORMS OF THERAPEUTIC ACTION 49 

fore, functional medication. If we constipate in periton 
our object is to immobilize the intestine, thus :iing diffu- 
sion of the microbes and extension of the inflammation, and 
soothe the pain; this is rather reparative therapeutics. 

oe of the procedures of naturistic therapeutics seems :: 
respond to a special indication requiring the exaggeration 
of a functional disorder, since such indication would invite 
the same objections that can be applied to a group of remedies 
of which I shall speak. 

It has been believed at all times that certain drugs cure 
by provoking a disease. Hippocrates' aphorism, trans! i 
into Latin, "duobus laboribus, simul, sed non in eodem loco 
obortis, vehementior obscurat alterum," has remained as the 
basis oi tins doctrine. It has not sufficiently been noted, 
I am sure, that the word vehementior implies that, by defini- 
tion, the remedy should be w rs than the evil for. in : 
no one would ever desire to induce a lesion of such a char- 
acter in a case of meningitis, tetanus, pneumonia, or pc 
onitis. But while the precept is not rigoro - plied, the 

doctrine which it rep: - te is ardently defended by some 
excellent minds. It is not more than a quarter of a century 
since 1 ssagrr - who was an eminent therapeutist, wrote: 
"The niedieanie: - impression upon the organism 

by a specific se (since its cause, the niedieanie: - eei- 

a disease which does not substitute itself for the real 
under treatment as homoeopaths believe, but the symp- 
toms ;urative acts of which the 

Qomy may ant age in recovering from the morbid 

and - laid down a fist of nosopoietic 

medioi: - responding to this conception and including ru- 

4 



50 PRINCIPLES OF THERAPEUTICS 

befacients, revulsives, caustics, emetics, purgatives, deliriants, 
convulsivants, paralysants, pyretogenetics, emmenagogues. 

Fonssagrives' conception contains an element of truth; it 
points out the analogy of medicinal to morbid action and 
is fairly applicable to organic and functional therapeutics; 
but his conclusions as to the formation of a class of nosopoietic 
medicines seems to us inadmissible. We do not believe, in 
fact, that there is in any of these medicines the example of 
a morbid action utilizable because of the fact that it is morbid, 
unless one is satisfied by the mydriasis produced by atropin 
and myosis by eserin. In the generality of cases it would 
be truer to state that the useful effects are produced in spite 
of the morbid effects and not by them. 

NOSOPOIETIC THERAPEUTICS 

The so-called nosopoietic medicines represent the last 
effort of physiological therapeutics according to which the 
efficacy of a medicine is always derived from its physiological 
action. We shall subsequently discuss this doctrine; it will 
suffice for the present to demonstrate by a few examples that 
useful effects are independent of morbid effects. This will 
lead us to the conclusion that the morbid effect is accessory 
and must not be considered as characteristic of the thera- 
peutic procedure; that, consequently, there is no nosopoietic 
any more than naturistic therapeutics. 

Let us take the case of vomiting caused by an emetic ad- 
ministered for the purpose of evacuating a poison. Is it 
not certain that if we could avoid the vomiting, morbid effect, 
and replace it by simple lavage of the stomach, inoffensive 
action, and at least as efficacious, we would secure the use- 



THE FORMS OF THERAPEUTIC ACTION 51 

ful effect without the addition of a morbid phenomenon? 
The latter is therefore accessory; what counts is the evacuat- 
ing phenomenon, i.e., an etiocratic or reparative therapeutic 
procedure. 

Revulsion has at all times been the classic example of a 
provoked morbid phenomenon curing another morbid phe- 
nomenon already existing. Is this interpretation exact? 
Can it be said that the usefulness of revulsion is due to the 
lesion so produced? Revulsion induces effects of two orders: 
some, functional, at distance; others, local. The former seem 
far less important, as I have elsewhere endeavored to demon- 
strate; the latter, probably the only useful, consist in leuco- 
cytic infiltration which seems to stimulate the phagocytic 
defense. If this interpretation is true, it is quite evident 
that it is not the morbid effect that is therapeutic but the 
phagocytic activity induced by it. Perhaps injections of 
nucleinate of soda or of colloidal metals will stimulate the 
desired activity without intervention of any morbid effect. 
The revulsive wound would then be deprived of its character 
of useful lesion. 

It is true that certain authors, Dr. Arnozan among others, 
have claimed for the revulsive wound another useful role: 
that of serving as a way of expulsion for the phagocytes filled 
with microbes and toxins and more or less ill-treated by their 
prisoners. This view has nothing illogical; but, if it were 
proved, it would establish simply that the organism takes 
advantage of an abnormal way of evacuation to rid itself of 
certain waste or dangerous elements. It would not demon- 
strate that the morbid process turned to benefit is a neces- 
sity, for we can imagine some other therapeutic procedure 



52 PRINCIPLES OF THERAPEUTICS 

by means of which the leucocytes would not succumb, but 
would, on the contrary, succeed in destroying, by digestion, 
microbes and toxins gathered by them, and consequently 
would not need to be expelled. 

The morbid process called forth is, therefore, unnecessary; 
it is endured by the organism, and when we utilize the revul- 
sion it is not at all because it is morbid, but in spite of its 
being morbid. 

More specious would be the argument derived from ther- 
mal elevations produced by certain therapeutic procedures 
truly pyretogenic (such as injections of physiological salt 
solution or of electrargol), and at times followed by a notable 
improvement. It is not unreasonable to believe that this 
rise in temperature may of itself prove useful, which would 
warrant application of the term nosopoietic to the procedure. 
This mode of action, however, is neither the only nor the 
principal one. It is always difficult to discuss therapeutic 
procedures that have multiple actions some of which are yet 
obscure. Does the injection of physiological salt solution, 
for instance, constitute a purely functional medication, pro- 
ducing nothing but an elevation of blood tension, increase in 
diuresis and stimulation of the nerve centers, as is supposed 
by Dr. Arnozan; or has it a paraspecific value, viz., etio- 
cratic, due to concomitant action on the elimination of cellular 
or other poisons, and on the leucocytic activity, at the same 
time a reparative value, owing to action on metabolism and 
on cellular reactions? It is very probable that the febrile 
reaction does not result solely from action on the thermal 
centers, but, at least in part, from increased cellular activity 
under the influence of direct stimulation which promotes 



THE FORMS OF THERAPEUTIC ACTION 53 

exchange and elimination and favors chemical combustion 
and transformation. 

What in the midst of these multiple activities is the febrile 
reaction taken by itself? It accompanies them mostly as 
an evidence of their intensity; but are we warranted in saying 
that, of itself, it plays a role sufficiently important to fur- 
nish the basis of interpretation? The reply is not doubtful. 

We must, therefore, dismiss the idea of a disease induced 
for the purpose of curing another disease already existing, 
namely, naturistic and nosopoietic therapeutics. We shall not 
abandon the practice of certain procedures of recognized 
utility, but we shall interpret their action otherwise than 
heretofore; we shall not seek the artificially produced morbid 
state for itself; we shall endeavor, when possible, to attenuate 
it or substitute for it inoffensive means serving the same end. 
Thus it is by no means necessary to bring about the reaction 
to which large doses of collargol and electrargol give rise; we 
have a hundred times obtained the beneficial effects of these 
medicines with small doses. 

These discussions prove that therapeutics is yet far from 
perfect and that our ideas of the mode of action of certain 
medicines are uncertain and disputable. It seems to me, 
however, that if all the therapeutic agents with well-known 
modes of action can be classified in one or the other of the four 
categories we have established, there is no advantage in open- 
ing for the others hypothetical categories. The probabilities 
are that the number of natural reactions is not very great or, 
at least, that these reactions obey laws which are small in 
number. We run, therefore, no great risk in contenting our- 
selves with the categories established in accordance with 



54 PRINCIPLES OF THERAPEUTICS 

rigorously demonstrated ideas, along with provisional groups 
attached to them, to be modified as further and more con- 
clusive knowledge is obtained. The important thing is to 
have the mind open to all the advancements of the science and 
to accept, without resistance or obstinacy, the demonstra- 
tion of new truths, even though these should disagree with 
our life-long convictions and habits. 



CHAPTER III 
OF THE ACTION OF MEDICINES 

Toxic action — Health and disease — Physiological action — Therapeutic 
action — Pharmacotoxinic synergy and antagonism. 

It is not our intention to make expositions of the classical 
notions relative to medicamental action, notions that are 
commonly found in Treatises of Therapeutics; we shall define 
the meaning only of the expressions: toxic, physiological, 
therapeutic actions, and study the more delicate question of the 
relations of therapeutic to toxic action. As a corollary, we 
shall take up, in a special chapter, the question of doses. 

TOXIC ACTION 

What is a toxic action f This question may seem to be a 

commonplace one, and yet it is not uncommon for authors to 

attach quite a different sense to this term. With a few of them, 

and those not of the least, the idea of death is confounded with 

that of toxicity. The name toxic equivalent has even been 

given to the dose which kills one kilogram of living matter. 

The word toxic is, however, synonymous with poison and 

the latter, as a matter of common agreement, is applicable 

to substances which, in small doses, 1 are capable of producing 

structural alterations or functional disorders of a more or less 

grave character, or death. Toxicity thus conveys a far more 

1 We must maintain a distinction between substances easily toxic (toxic 
in small doses, true poisons) and those requiring large quantities, such as 
chlorid of sodium. 

55 



56 PRINCIPLES OF THERAPEUTICS 

extended idea than that usually attributed to it. It comprises 
all the degrees of harmfuhiess, from the slighter ones to those 
most rapidly fatal. The expression toxic equivalent, to desig- 
nate the fatal dose, is not, therefore, altogether correct. The 
dose that kills must simply be called fatal dose, which defines 
itself, and winch can conventionally be related, if so desired, 
to the kilogram of living matter of a determined animal. 
It is understood that by that will be meant the minimum fatal 
dose and that this will vary, not only with the animal experi- 
mented upon, but also with the mode of introduction of the 
poison, its degree of concentration, the technic employed, and 
even, at times, with the manufacturer who prepared the toxic 
substance. 

In what dose must a substance be considered toxic? The 
first toxic phenomenon is as difficult to perceive as the first 
disturbance of health. The sagacity of physicians of all 
epochs has unsuccessfully been applied to defining disease. 
In order to. define disease, it would be necessary to compre- 
hend exactly in what health consists; but the latter is con- 
founded with the conception of life whose essence eludes com- 
prehension. We are therefore compelled to forego precision. 

Health and Disease. — It is necessary, however, in order to 
understand the value of the terms toxic and physiological, 
as well as the action of medicines on the organism, to form 
a conception as exact as possible of disease and of health, in 
the present state of science. 

Life obeys laws which are analogous in the healthy and 
in the sick. The differences between the two are due to 
changes which the intervention of a morbid cause creates 
in the metabolism and reaction of the living matter. In the 



OF THE ACTION OF MEDICINES 57 

sound organism there is a state of equilibrium and fixity of 
functions and organic systems, because the living matter is 
adapted to the almost invariable excitations, which it receives 
in the course of normal life. Conversely, in the diseased 
organism, this equilibrium and fixity are disturbed because 
the living matter undergoes the influence of endogenous or 
exogenous causes, to the impression of which it is not and 
often cannot be adapted. The result is that the reactions 
through which it responds to them are expressed in the form 
of new (so-called morbid) manifestations of life. This is 
not all; the impression of these causes upon the living matter 
may exceed the degree of resistance of the latter and inflict 
upon it structural alterations; namely, lesions, which in some 
cases may be due to other causes, particularly to excessive 
intensity of reaction. Moreover, the functions which are 
carried on in health in a determined manner by the struc- 
ture and chemical composition of the living matter and its 
medium, will be disturbed if this structure be altered or this 
composition adulterated. It is lastly to be noted that the 
functional trouble may, in its turn, affect the living matter 
and become a cause of lesion. 

In brief, disease is constituted by three sorts of elements: 
1. Abnormal reactions of the living matter, for instance, fever, 
inflammation. 2. Structural lesions which, however, may be 
absent or not appreciable, and which, when present, are pro- 
duced either by the intensity of the effect of the morbid cause 
upon the living matter, or by the strength of the latter's re- 
action, or else by the disturbance of functions. 3. Functional 
disorders resulting from abnormal reactions, adulteration of 
chemical composition of the cellular elements or their media, 



58 PRINCIPLES OF THERAPEUTICS 

and, lastly, from structural lesions of the living matter. 
Renal, cardiac, hepatic insufficiency, paralyses, etc., are exam- 
ples of such functional disorders. 

The state of disease will last until the living matter has 
accomplished its task of eliminating or destroying the morbid 
cause or adapting itself to its impression (when such adapta- 
tion is possible); only thus will be effected the re-establish- 
ment of the equilibrium and fixity of its evolution, char- 
acteristic of health. 

One may, therefore, thus define disease: the disturbance 
of the habitual organic equilibrium by the fact of an abnormal 
force acting with sufficient intensity to modify the fixity of its 
reactions, the habitual play of its functions and at times its 
structure and chemical composition, thus giving rise to dis- 
orders which persist until the accomplishment by this living 
matter of elimination or destruction of the modifying cause or 
else its own adaptation to the presence of the disturbing 
force. 

This conception of disease will enable us to define toxic ac- 
tion, which, in reality, is one of the causes capable of exerting 
an abnormal effect upon the living matter and modifying its 
reactions, functions, and at times its histo-chemical structure. 
And here, the cause being readily recognized, the analysis of 
its effects will be simplified. Chloroform anesthesia, for 
instance, is a true intoxication which produces reactional 
disturbances (period of excitement), functional disturbances 
(disappearance of sensibility and muscular resolution), and 
even lesions (lesion of certain cells of the renal convoluted 
tubes). It behaves, therefore, like a disease which disap- 
pears when elimination of the chloroform is complete. Like- 



OF THE ACTION OF MEDICINES 59 

wise, alcoholic intoxication may be considered as a disease 
expressed, in its slightest degrees, by exaggerated reactions 
and, in its gravest degrees, by functional disorders accom- 
panying the reactional disturbances. 

The analogy is extended beyond the cases in which the 
toxic action is the result of a large dose, as in the foregoing 
examples. As there is an insensible transition between the 
state of health and the state of disease, consisting in slight 
disorders which endanger neither the great functions nor 
the quietude of the individual, so the effect of a toxic sub- 
stance upon living matter passes habitually through degrees 
as numerous as it is possible to imagine and realize by means 
of successive dilutions, beginning with the very first effect 
appreciable to our means of investigation until death. Where 
does disease begin? Where does toxic action begin? We 
cannot tell with accuracy. 

There are even circumstances in which the modification 
induced in the living matter does not reveal itself by any 
immediate manifestation. It is only after impressions often 
repeated or prolonged that we succeed in recognizing, at a 
certain moment, structural or chemical alterations that have 
silently been established. Here also toxic action is com- 
parable with morbid action; thus the slow action of alcohol 
taken to excess, accumulating silently the arterial altera- 
tions, does not differ from endogenous influences which pro- 
duce the same progressive alterations. In both cases there 
is a latent period during which hea th does not seem to be 
endangered while lesions are in course of slow formation, 
viz., the living matter is undergoing a change in its equi- 
librium and fixity, 



60 PRINCIPLES OF THERAPEUTICS 

Nevertheless, the mechanism by toxic action is far more 
frequent than by true morbid action. Is there anything 
more insidious, from this standpoint, than the action of cer- 
tain hypnotics? Take, for instance, the case of a woman 
who has been using for months or perhaps a year a daily dose 
of sulphonal without alteration in the living matter being 
betrayed by any modification; and yet there may suddenly 
supervene grave disorders liable to end in death. 

The formation of these latent alterations remains unnoticed 
until the tardy effects compel attention. This is explained 
by the fact that the morbid or toxic state is more readily ex- 
pressed by the reaction of the living matter or by functional 
disturbances than by a lesion. The latter may exist even 
in the absence of any disease properly so called : thus an ori- 
ficial lesion of the heart, if well compensated, may be per- 
fectly tolerated and give rise to no functional disorder what- 
ever. It is conceivable, therefore, that by the side of a 
more or less noisy toxic action there may exist another action 
slowly and silently working its ravages, without any ap- 
preciable reaction of the living substance or marked func- 
tional disturbance, to end in the production of a lesion or 
alteration which will not be revealed until it has attained 
a certain stage of development (alcoholism, arsenicism, etc.). 

At times the toxic action is developed in the course of a 
morbid state, only after a phase which may have seemed free 
from danger or even favorable. This special action is not 
infrequent after the administration of certain antithermics, 
notably antipyrin, to sufferers from fever, particularly in the 
aged, young children, neurasthenic, depressed, or nervous 
persons. At first the temperature goes down and the patient 



OF THE ACTION OF MEDICINES 61 

experiences momentary relief, but soon he is overtaken by 
chills, vertigo, and general malaise; instead of the habitual 
return of the high temperature there appear hypothermia 
attended with cold sweating, collapse, or even a comatose 
state; in extreme cases the situation grows worse, the patient 
is cyanosed and dies. Here the action is complex: it involves 
both the nervous system and the heart, but the fact of the 
febrile state is fundamental because accidents of such gravity 
are not observed in apyretic subjects. 

These secondary toxic effects are by no means rare. At 
the epoch when tartar emetic was often prescribed in pneu- 
monia, a state more or less grave of collapse was frequently 
observed (at times even after apparently favorable effects). 

As regards the work which the living substance is capable 
of when affected by a toxic substance, nothing is more remark- 
able than the example of morphin. The latter is at the same 
time transformed (morphetin and oxydimorphin) and elim- 
inated, but if the impression be renewed, the living matter 
little by little adapts itself thereto and finally creates a ficti- 
tious equilibrium into which the morphinic impression enters 
as a necessity, so that if this impression ceases the equi- 
librium is again disturbed and the living matter manifests a 
state of disorder. 

In the case of other toxic substances complete destruction 
occurs; such is the case with sulphonal. It is therefore true 
that a toxic substance behaves like a morbid cause. But 
here we would be able to avoid the toxic action, if we possessed 
a characteristic of its measure, by keeping ourselves this side 
of the harmful dose. Unfortunately, as we have seen, this 
measure is often wanting; the only one we have, more in- 



62 PRINCIPLES OF THERAPEUTICS 

teresting from the standpoint of toxicology than from that 
of therapeutics, is that of the effects which follow large doses; 
but the action of relatively small doses may be insidious, slow, 
or secondary, and lead to fatal mistakes. Hence, in prac- 
tice, the necessity of always remembering the toxic action, 
especially when the medicine prescribed may exert an effect 
upon the heart or the nervous system, or upon a subject in 
a state of depression, of natural feebleness (childhood, old 
age), or of great susceptibility (nervous), when it acts upon 
an organ already attacked by disease (intoxicated heart, or one 
stricken by myocarditis), when the ways of elimination (kid- 
neys, digestive canal) or transformation (liver) are involved, 
lastly when long continued medication may inspire fear as to 
the effects of accumulation or tolerance. 

In brief, toxic effect is a morbid state which differs from 
other diseases only by the specificity of its cause. As disease, 
so a toxic effect is more or less acute, more or less grave; like 
it, it may be established silently, and is hard to discover when 
developing within the confines of health, and it is impossible 
to characterize it otherwise than by its intensity, duration, or 
gravity. 

We shall therefore define toxic action: the action upon the 
organism of any substance which, in a relatively small dose, is 
capable of producing reactional, material, or functional disorders, 
remarkable by their intensity, duration, or gravity, whether these 
disorders be immediately appreciable, or secondary and more 
or less slow in development. It is now obvious how far we are 
from an equation between toxicity and death. 



OF THE ACTION OF MEDICINES 63 



PHYSIOLOGICAL ACTION 

But medicines may modify the organism within limits not 
exceeding normal physiological reactions, viz., without dis- 
turbing the equilibrium and fixity which constitute the state 
of health. The effects produced by them are then without 
danger, easily manageable and consequently of great help 
when we wish to correct a morbid condition whose persistence 
or intensity seems dangerous. 

It would be of great importance to differentiate this from 
toxic action, less interesting from the view-point of therapeu- 
tics than from that of experimentation. Unfortunately, 
experimenters have taken very little trouble to study the 
effects of small doses, which only are useful. They have not 
even thought of giving a special name to the medicinal action 
when it does not attain toxicity; or rather they have included 
it, along with the toxic action, under the generic term of 
'physiological action; indeed, all treatises on therapeutics 
describe, in the chapter on physiological action and under 
that name, the toxic disorders caused by medicaments. 

There is an excellent reason for this manner of procedure: 
the laws of normal physiology do not differ from those of 
pathological physiology, and physiology has extended its 
limits to all the normal or abnormal modes of action of the 
organism. There is, however, this difference between normal 
and pathological physiology: one studies the properties of 
the tissues and functions of the organs in a state of health, 
while the other is devoted to the study of morbid reactions 
produced by a pathogenic cause. It would have been alike 



64 



PRINCIPLES OF THERAPEUTICS 



correct and useful to differentiate the medicinal doses the 
reactions of which do not exceed the limits of normal re- 
actions, from those which give rise to toxic reactions. It 
would have sufficed, for this purpose, to reserve for the 
former the name physiological and give the latter the desig- 
nation toxic. Toxic effects would then be easily differen- 
tiated from physiological. 

But usage has decided otherwise. The physiological action 
of medicines comprises the action of all doses upon the tissues, 
organs and functions, whatever the effect produced, and we 
have no word to express that a substance modifies a function 
or the properties of tissues within the limits of normal reactions 
of the living matter. We propose that of utilizable action, 
different, as we shall see, from therapeutic action, which 
does not always result from a physiological action. 

These distinctions are by no means theoretical subtleties; 
they have a practical importance of the highest order. Experi- 
menters will no longer exhaustively investigate the toxic 
action of a substance; on the contrary, the utilizable actions 
will interest them. Let us consider, for instance, the various 
degrees of action of the same substance in increasing doses 
but with a very slight difference between them. We may at 
first fail to observe any appreciable effect; next we shall 
produce effects which do not exceed the limits of normal 
physiological variation; and with more and more increased 
dosage we shall notice the appearance of toxic effects, first 
curable, and then fatal. 

Let us take the case of a man who ingests l/10mg. 
of strychnin. No effect will be manifest, but as soon as 
a dose of 1/2 mg. and, a fortiori, 1 or 2 mg. is reached, 



OF THE ACTION OF MEDICINES 65 

there will appear effects within the limits of normal equi- 
librium (stimulation of the gastro-intestinal apparatus, in- 
crease in the salivary secretion). Attaining the doses of 
3 to 5 or 6 mg., we find ourselves within the confines of 
utilizable effects and of toxic effects. Exaggerated reflexes, 
muscular twitchings, a sensation of muscular tension affect- 
ing the freedom of deglutition and respiration, hence anxiety 
of the subject, are undoubtedly physiological reactions but 
have exceeded the limits of those observed in health and 
deserve therefore to be called toxic. Should we reach the 
doses of 10 to 15 mg., we would find ourselves in the presence 
of tetanism; a still larger dose would endanger life; that of 
3 eg. would probably cause death. 

There are, therefore, in the action of strychnin, as in that 
of almost all medicinal substances acting on the organism, 
three distinct phases: 1. An exaggeration of phenomena 
consistent with the normal state; this exaggeration, being 
utilizable only from a functional standpoint, is this action 
which I call utilizable. 2. The development of phenomena 
which can be considered as toxic because of their intensity 
and gravity, and which are only exceptionally utilizable. 
3. Death. 

The problem of favorable medicinal intervention is in these 
distinctions. It has long been strongly believed that toxi- 
cological experimentation would render the greatest services 
to therapeutics. At a certain epoch practitioners hoped to 
cure a disease by modifying its symptoms through some ac- 
tion at times contrary and at other times similar; but it is 
now known how deceptive these methods are. Who to-day 
would think of imitating Trousseau who prescribed strychnin 



66 PRINCIPLES OF THERAPEUTICS 

in chorea until he attained tetanizing doses? Fonssagrives 
rightly declares that one of the most serious drawbacks to 
therapeutic progress is the abuse that has been made of the 
data of experimental toxicology to pharmacology. How has 
it been possible to hope, in fact, that the addition of a harm- 
ful action of toxic origin to a harmful action of morbid origin 
could produce a beneficia 1 effect? It is time to abandon 
these unreasonable confusions: u toxic action similar to mor- 
bid action" must be opposed by utilizable action or normal 
physiological action, simply modifying the normal physiolog- 
ical acts without trespassing the limits of health and being 
of a daily and valuable utilization. 

This utilizable action is the weapon of functional thera- 
peutics, and a knowledge of it is a safeguard against symp- 
tomatic therapeutics which cannot, without danger, be 
guided by the indications of clinical observation alone. 

THERAPEUTIC ACTION 

Utilizable physiological action and, exceptionally, toxic 
physiological action constitute the means which concur to 
the realization of the ends of medicine, viz., to cure or to 
favor recovery. In this application they come within the far 
larger range of therapeutic action which may be medicamental, 
hygienic, surgical, mechanical, physical, or even psychic. 

In its broadest acceptation the term therapeutic action 
comprises: all actions capable of producing either a curative 
effect, or a desirable functional modification, or a good 
symptomatic correction, or favoring reparation of a lesion or 
chemical adulteration or a defective dynamism. 

It is necessary to lay stress on the fact that a therapeutic 



OF THE ACTION OF MEDICINES 67 

action, even when exclusively medicinal, is not necessarily 
related to modification in the great functions of economy, 
as has long been taught. Thus, mercury and quinin, which 
have such powerful therapeutic action, may exert the maxi- 
mum of that action without producing the slightest appreci- 
able physiological effect, and, at all events, without any corre- 
spondence between that action and the more or less slight 
disturbances which are sometimes observed after their em- 
ployment. It is no longer believed that there is a relation 
between the curative action of mercury and stomatitis, be- 
tween the cure of malaria by quinin and the ringing in the 
ears. The same is true of all the agencies of specific thera- 
peutics, and sometimes even of symptomatic modifiers. Half 
a gram of antipyrin may cause a headache to disappear 
without any notable functional modification. It is simply 
through chemical correction that an alkali, neutralizing the 
gastric contents of an hyperchlorhydric subject, relieves 
the pain. It is rather as an aliment than as a physiological 
modifier that an organic phosphate promotes reparation of 
the organism. 

It is for these reasons that I have differentiated physio- 
logical action, whatever that may be, from therapeutic action. 
The latter is very often independent of the former, notwith- 
standing the opinion of the protagonists of scientific thera- 
peutics, namely, the majority of the first experimenters of 
the action of medicines on the organism, and their followers. 
The truth is that the functional modifications produced by 
medicines are utilized in view of functional and sometimes 
of symptomatic therapeutics. Still, it is by no means more 
or less toxic excessive actions that offer the most important 



68 PRINCIPLES OF THERAPEUTICS 

utilization, but the most moderate actions, those whose effects 
do not exceed the limits of normal reactions in a state of 
health, in most cases the stimulating actions (and on condi- 
tion that the stimulation is not to be followed by depression) 
or the actions which produce normal physiological effects 
(hypnotics). 

Therapeutic action may, though seldom, profit by a toxic 
action. General or local anesthesia, for instance, is a true 
intoxication. Atropinic mydriasis and myosis due to eserin 
belong in the same category. Besides these few examples 
it would be difficult to point out any well demonstrated ap- 
plication of toxic action. 

It may happen that a medicine cures or favors recovery, 
at the same time giving rise to phenomena bordering on tox- 
icity, but these are manifestations of intolerance, and the 
useful effect is obtained not through, but in spite of, them. 
The toxic effect of intolerance is secondary; we must strive 
to avoid it; the patient will then recover more readily. More- 
over, excepting the few cases above referred to, all we have 
said of natural and nosopoietic therapeutics is applicable 
to toxic action. 

The conflict between toxic actions of morbid origin and 
medicinal actions has given rise, under other names, to much 
controversy and to too little exact study. It is in part in 
regard to this conflict that the partisans of contraria con- 
trariis and those of similia similibus have carried on so much 
controversy. Once in a while the echo of these disputes is 
again heard, but no one takes any interest in them, because 
all a priori systems are questionable. Science accepts the utili- 
zation of contraries as well as that of similars, when it is effi- 



OF THE ACTION OF MEDICINES 69 

cacious. The only interest lies in the establishment of the 
conditions of this utilization and, for this purpose, it would 
be necessary to know exactly the action of medicines upon 
affected organs and particularly upon those which have under- 
gone morbid toxic action. 

When an organ is merely tired out through the exhaus- 
tion of its dynamism, there is no doubt as to the utility of a 
contrary action; it would even seem that all means are good, 
provided the action is proportionate to the needs. Thus a 
heart simply weakened, without being intoxicated, will react 
to all stimulants (caffein, spartein, etc.); the same is true of 
the nervous system which is benefited by the exciting action 
of coffee, kola, quinin in very small doses, strychnin, and 
alcohol. But the question becomes far more embarrassing 
if the anatomical element of the weakened organ has pre- 
viously received the more or less profound impression of a 
poison of morbid origin. 

PHARMACOTOXINIC SYNERGY AND ANTAGONISM 

In the absence of precise data on this subject, we are obliged, 
not wishing to overlook a question of such great importance, 
to reason by analogy and to be satisfied, for the time being, 
with probabilities. We are thus led to compare the action 
of medicines on intoxicated organs, an action which we will 
call pharmacotoxinic, with the action of medicines or of poi- 
sons upon organs which previously or simultaneously have 
been impressed by another medicine or poison. 

I believe there is a pharmacotoxinic synergy altogether 
comparable to medicinal synergy. A medicine reinforces the 
action of a poison of morbid origin when it hinders its elimi- 



70 PRINCIPLES OF THERAPEUTICS 

nation through the kidneys. Antipyrin, morphin, and can- 
tharides often produce this effect. In other cases pharma- 
cotoxinic synergy may be more direct, as, for instance, when 
strychnin is given to a tetanic person or chloral in uremic 
coma. In order to complete the analogy, one would find 
medicines, such as caffein, which, predisposing to insomnia, 
might favor the action of a toxin producing the same effect, 
as in the beginning of typhoid fever. It is hardly necessary 
to say that such synergies must be avoided, and that they 
establish numerous contra-indications. 

There is also a very clear pharmacotoxinic antagonism: 
any medicine capable of favoring elimination of a morbid 
poison, of exerting an action contrary to that of some other 
poison, or simply rendering an organ less sensitive to its im- 
pression deserves the name of pharmacotoxinic antagonist. 

But the questions concerning therapeutic antagonism are 
laid down here with a particular interest, for it is necessary 
to ask whether a medicinal action, antagonistic in appear- 
ance, added to a toxic action of morbid origin, will remain 
antagonistic or whether it will, on the contrary, be apt to 
reinforce the latter by addition of toxicities, or simply be 
powerless. 

It is not superfluous to bear in mind first that the only 
characteristics of toxicity are the intensity, duration, and 
gravity of the reactional phenomena produced by a substance; 
so that the question is one of degree between the toxic and 
the medicamental reaction. This is so true 'that the mere 
addition of the two actions, even moderate, may become 
toxic: thus sufficient doses of chloroform and morphin, 
while separately incapable of abolishing sensibility, induce 



OF THE ACTION OF MEDICINES 71 

anesthesia when simultaneously administered. One dose of 
ipecacuanha and one of tartar emetic, each insufficient to 
produce vomiting, will cause it if they are associated. A 
quantity of absinth (liquor), capable of causing intoxication, 
is composed of various elements (alcohol and various essences) 
which, taken separately by the same subject, would generally 
have no such action. The addition of a medicine in an in- 
nocuous dose to a morbid poison may also prove detrimental 
if the two substances are synergic. It is undoubtedly partly 
for this reason that typhoid patients are so badly affected by 
hyposthenizing drugs and digitalis. 

We must next turn to the study of medicamental and toxic 
antagonists and see what happens when we utilize them. 

True antagonism should be distinguished from false or 
apparent. True antagonism refers to two substances which 
produce opposite effects upon the same anatomic elements 
or the same organs. The study of this antagonism has given 
rise to the most contradictory assertions. There is, however, 
one conclusion which admits of no doubt: antagonistic ac- 
tion is not merely a neutralizing one; the impression exercised 
by the two substances on the anatomical elements leaves 
one resultant, so that if the doses are increased, death certainly 
would result. Therefore the purest and truest antagonism 
has its limitations. 

These limitations have several causes. The most impor- 
tant, from the view-point under consideration, results from 
the effect exerted by the first substance which has affected 
the anatomical element. If this effect is sufficiently intense 
to cause death, it creates a true inertia to the action of the 
antagonistic substance. This is what Prof. G. Pouchet has 



72 PRINCIPLES OF THERAPEUTICS 

called the possession of the cell by the toxic substance or elective 
affinity or impregnation and which I have designated under 
the name adherence of the poison to the cell. This adherence 
profoundly modifies the reaction of the cell to the antago- 
nist. If the latter is employed in small or in average doses 
reaction will be nil or inadequate; if large doses are employed, 
the antagonistic impression will simply overcharge the ana- 
tomical element and be added to the toxic influence. It 
is only in cases in which the cell is not irremediably affected 
that it is possible, through an antagonistic action, to give 
the poison time to be eliminated and the cell time to resume 
adequate activity. 

When a morbid poison has taken possession of the elements 
of an organ, it has seemed to me, clinically, that the active 
medicines which were sometimes opposed to it, behaved as 
badly as the so-called antagonistic substances. Given in 
small doses, they no longer produce their effects ; given in large 
doses, they 'aggravate the situation, as though the medica- 
mental impression was added to the toxic action, or as if it 
favored exhaustion of the cell. This exhaustion through 
toxic action forms a new limitation to the medicamental 
action. This fact requires the most careful attention for 
the reason that a large dose of a medicine often produces an 
action contrary to that of small or average doses (which doses 
one has generally in mind when speaking of the medicine), 
and that the large dose then easily becomes synergetic with 
that of the morbid poison. Quinin and digitalis which, in 
small doses, strengthen the cardiac contraction, weaken 
it in very large doses. What are we to expect from the latter 
in cases of cardiac asthenia? Clinically, digitalis and quinin, 



OF THE ACTION OF MEDICINES 73 

in doses even moderately large, produce dangerous effects 
on the hearts of typhoid and broncho-pneumonia patients, 
when possession of the organ by the morbid poison is ex- 
pressed by embryocardiac rhythm or by suppression of one 
of the heart soimds. 

Pharmacotoxinic antagonism is therefore utilizable only 
in cases of acute or chronic, but not severe, morbid intoxi- 
cations, namely, in those cases in which it is probably useless. 
In serious forms, it is dangerous and no more likely to 
prove efficacious, from the therapeutic standpoint, than is 
true toxic antagonism in intoxications. It does not prevent 
the pharmacotoxinic overcharge. 

Is the same true with regard to apparent or indirect an- 
tagonism, namely, that which produces contrary effects 
through some procedure or mechanism? It is evident that, 
if the two actions are toxic, they are sure to be added to each 
other in the same subject. In order that this indirect an- 
tagonism be useful, the therapeutic action must not be too 
intense and must then intervene either after the manner 
of a symptomatic agent to prevent the toxic symptom from 
becoming dangerous of itself, or in order to support life until 
the organism has had time to eliminate the poison. This 
antagonism is "far less dangerous than the true one; all that 
is necessary is that the superadded action be not dangerous 
of itself; then it will do no harm and no cumulative action 
is to be feared. But this antagonism also has its limits, 
since it exerts no direct action on the cause of the intoxica- 
tion itself. Just as it is, however, apparent antagonism is 
not to be ignored: through its action it is often possible to 
prevent death by asphyxia or syncope, and thus give the 



74 PRINCIPLES OF THERAPEUTICS 

organism time to overcome the poison through its system of 
defensive measures. 

From the pharmacotoxinic standpoint, apparent antago- 
nism is very interesting. It renders possible functional 
intervention without adding to the toxinic effect that of a 
medicine upon the same elements; it is, therefore, preferable 
to resort to it. For instance, when the myocardium is weak- 
ened by a morbid poison, if no medicine can act as an anti- 
dote or true antitoxin, it is far more preferable to sustain the 
heart by an action bearing upon the nerves of that organ (such 
as that of spartein) than by an action affecting the cardiac 
fiber itself, as does the poison. We have given and will still 
give numerous examples of this indirect functional action. 

It is to be recognized that these considerations, calculated 
to render one very prudent in the employment of active medi- 
cines, especially in large doses, in the treatment of patients 
whose organs are deeply affected by morbid poisons, would 

be incomplete if we should not add that their deductive char- 

- 

acter restrains their value. Our main purpose is to call at- 
tention to the possibility of doing harm through the addition 
of medicinal to morbid toxicity. 

We must also add that it is by no means impossible that 
certain medicines play the part of antidotes in regard to cer- 
tain poisons. In plain pneumonia, for instance, digitalis 
has a good action which is not questioned and which it pos- 
sesses to the exclusion of other cardiotonics. Hence, some 
have (Landouzy) attributed to it, not without probability, 
an antitoxic role against the toxins of pneumonia. Actions 
of this nature are probably quite rare, and, at all events, 
none has hitherto been demonstrated. But a drug may 



OF THE ACTION OF MEDICINES 75 

have an action very different from a purely functional one: 
it may arouse processes of defense, act after the manner of 
ferments (the fresh leaves of digitalis contain an oxydase), 
supply substances deficient in the organism, play the part 
of a protective substance, or, lastly, by reaction cause the 
production of these substances. These processes are just 
beginning to come to light and no one can tell the import- 
ance they will assume in the future in the interpretation 
of therapeutic actions. 

It may furthermore be supposed that the introduction of 
a foreign toxic element into the interior of the living matter 
would have the power to produce therein such a reaction 
as would at the same time stimulate the organism to free 
itself of the morbid element. This would be a form of the 
substitutive therapeutics of the ancients. Such perhaps is the 
mode of action of tuberculin which, inducing in the infiltrated 
tissues an excessive reaction, would emphasize the defense of 
the living matter. It is to be noted, however, that, in so speak- 
ing, we are in a purely hypothetical domain and that, at all 
events in case of tuberculin, the very vitality of the ana- 
tomical element is engaged to such a degree that, if the 
reaction is exaggerated, it expresses itself by necrosis. We 
cannot say, therefore, that the action must be toxic in order 
to be useful. 



CHAPTER IV 
DOSES 

Bases for determination of doses and criticism of systematic doses — 
Specific doses — Functional doses — Symptomatic doses — Reparative doses. 

BASES FOR DETERMINATION OF DOSES: SYSTEMATIC 

DOSES 

Therapeutic action utilizes the effects of medicaments ac- 
cording to a gradation obtained through the handling of 
doses. Therapeutic doses are to be more or less large ac- 
cording to the end in view, the state of resistance of the 
patient, the form of the medicament and, lastly, the mode 
of introduction of the latter into the system. We shall first 
study the relation of doses to the end to be obtained. 

Posology is the more highly interesting as the classical data 
on this subject are quite uncertain. The doses recommended 
by authors are most variable, some advocating very large 
doses bordering on toxicity (physiological therapeutics), 
others contending that infinitesimal doses are more useful 
(homoeopathy). 

The rule cannot be single and the dose must vary with 
the indication to be realized. In a general way, however, 
it may be stated that an unfortunate tendency to prescribe 
too large doses has always prevailed. The homoeopaths have 
rightly rebelled against these, and it is very probable that 
they have not infrequently succeeded where their allopathist 
rivals have failed, either because their infinitesimal doses 

76 



DOSES 77 

were negligible and consequently incapable of impeding spon- 
taneous recovery, or because they served as useful auxiliaries 
in modifying the disturbed functions in a modest measure 
and without danger. 

The reasons which have actuated physicians to prescribe 
large doses have varied with the epochs, but they have always 
been theoretical. Anciently, certain interpretations, which 
have since been shown to be erroneous, seemed to justify the 
partisans of large doses. For instance, mercury was at a 
certain epoch administered to cause stomatitis and saliva- 
tion for the purpose of favoring expulsion of the morbid ele- 
ment. When the administration of emetic in pneumonia 
produced prostration, the phenomenon was believed to be 
an effect of tolerance. At a later period the employment 
of large doses seemed to be warranted by the doctrines of 
physiological therapeutics. In the belief that medicines 
cured by their physiological action, the doses were raised 
until appreciable reaction, even toxic phenomena were pro- 
duced. It was even asserted that there was no truly useful 
dose but the largest tolerated; hence the colossal doses of 
strychnin (enough to produce muscular rigidity), of caffein 
(often ending in delirium), of antipyretics (having the pre- 
tention of curing, and, in the face of obvious failure, that of 
causing disease to evolve without fever), of creasote, anti- 
pyrin, sodinin salicylate, mercury, etc. 

At the present day another interpretation is leading to 
the prescription of large doses of certain so-called specific 
remedies. The demonstration of specificity, which was still 
a subject of dispute as recently as thirty years ago, has en- 
gendered the belief that these remedies act directly upon 



78 PRINCIPLES OF THERAPEUTICS 

the pathogenic agent. We may suppose, considering the 
constancy and rapidity of the curative effects, that the patho- 
genic agent is influenced by the specific medicine, but we 
cannot deny to the organism a certain participation in the 
struggle against the disease germ. It is true that this par- 
ticipation does not consist in modifications in the great func- 
tions, but it is in no wise impossible that it should lie in an 
action upon the means of natural defenses of the organism. 
We must, therefore, be satisfied with mere conjectures to ex- 
plain the mode of action of specific drugs. Whatever the 
value of these conjectures may be, it has been imagined that, 
since medicines are supposed to act upon the pathogenic 
cause, there was advantage in prescribing the largest doses 
tolerated by the organism. There have been some physi- 
cians who, by a singular abuse of generalization, have ex- 
tended this formula to all medicines. 

Like all simplified views, this one has appeared seducing, 
and like all views of the mind, it is contestable and in great 
part inexact. If this principle were followed to the letter, 
10 grm. of antipyrin and as much as 12, 15 and 20 grm. of 
salicylic acid, which are tolerated by many a patient, should 
be administered in rheumatism — doses against which com- 
mon sense protests. Think of possible doses of quinin, iron, 
phosphates, etc.! 

I have more than once denounced 1 this formula of the 
largest dose tolerated, and have argued that instead of it 
the smallest efficacious dose should be prescribed, the deter- 
mination of which is no deduction from hypotheses, but the 

1 Societe med. des hop. de Paris, February 14, 1896, and especially 
Province Medicate, November 17, 1906. 



DOSES 79 

result of clinical observation. I admit, at the same time, 
that the smallest efficacious dose may be relatively large 
and, in certain cases, it may approach intolerance. When 
the question is, for example, one of expelling tenia by means 
of pelletierin, it not infrequently happens that the necessary 
dose produces vertigo. Sodium salicylate, in acute artic- 
ular rheumatism, is not truly curative except in quite large 
doses. If it is necessary to touch the border-line of toler- 
ance for curing, I do not object, but I make this concession 
impelled by demonstrated necessity and not at all in the 
name of an imaginary principle. 

The reasons which I have adduced against the largest dose 
tolerated by the organism are the illogicalness, danger, and 
habitual uselessness of this practice. I say it is illogical to 
lay down an a priori principle independent of observation 
of therapeutic effects. It is not argued, in fact (which would 
at first sight appear as a principle of good sense), "the dose 
capable of curing the sick shall be given"; the formula is: 
"the maximum dose tolerated shall be given." But why 
give a dose X, derived from the knowledge of the effects of 
intolerance, if the dose X-x is sufficient to cure the patient? 
Undoubtedly, this is an application of the proverb: "What 
can do the greater, can do the lesser"; but proverbs do not 
constitute scientific methods; rigorously observed facts alone 
must guide us. I say, furthermore, that the largest dose toler- 
ated by the organism is dangerous because the phenomena 
of apparent intolerance do not express the measure of the 
noxiousness of a remedy. The cellular protoplasm may, in 
fact, suffer grave alterations without any manifest disturb- 
ance of health, and yet these alterations will be revealed 



80 PRINCIPLES OF THERAPEUTICS 

under certain circumstances by increased vulnerability of 
the system: thus great infectious diseases are of exceptional 
gravity in mercurialized subjects (A. Robin); topers often 
show the first signs of alcoholic ravages on the occasion of 
some traumatism or an acute disease; diabetic subjects may 
be ignorant of their diabetis until an accident suddenly reveals 
their diminished resistance. Besides, it is impossible con- 
stantly to approach the lines of intolerance without some- 
times crossing them. Lastly, many morbid phenomena 
yield to average doses of specific remedies far short of 
the largest doses tolerated (syphilitic symptoms, intermittent 
fever, acute articular rheumatism). 

The advocates of excessive doses pretend that such doses 
enable them to cure not simply the symptoms but also the 
disease itself (abortive treatment of syphilis). This ques- 
tion being under study as regards syphilis, it is impossible 
to give a definite opinion. If it were demonstrated that the 
maximum doses of mercury are capable of aborting syphilis, 
they should certainly be prescribed, even at cost of certain 
dangers. But the demonstration would have been made 
only as regards syphilis and in no wise with regard to other 
diseases with specific treatments. The rule to be followed 
would then be derived from clinical observation and not at 
all from the principle of the largest dose tolerated; and there 
would be no escape for anyone, in the name of any reasoning 
whatever, from the teachings of facts. 

Large doses are permissible in certain cases of pernicious 
malaria and malignant syphilis, in which it is necessary to 
prescribe at once, but temporarily, such considerable amounts. 
It is likewise possible in the case of a vigorous subject, who 



DOSES 81 

is free from organic taint and has received no treatment, or 
after an interruption of treatment, to prescribe with advan- 
tage large doses which will prove the more efficacious as the 
pathogenic agent has undergone no habituation to the medi- 
cament and. as the organism of the patient is in possession 
of all its forces of resistance. But these large doses must be 
reduced as soon as they have produced then maximum effect. 
Exception is to be made with certain drugs such as potassium 
iodid which require prudent testing of the tolerance of the 
patient, in order not brutally to give rise to accidents of grave 
intolerance. 

SPECIFIC DOSES 

In good therapeutics the doses must be proportionate to 
the object in view. To a specific disease (syphilis, malaria, 
acute articular rheumatism) are to be opposed doses which 
will always be relatively large (specific doses) and determined 
by clinical observation. 

This observation is at times very delicate; it requires 
much attention, time, and circumspection. Is it not strik- 
ing to see, at the present moment, the best clinicians of 
France and Germany unable to fix the dose of atoxyl to be 
employed in syphilis? It is only after numerous and scru- 
pulously studied observations that one can establish the doses 
always tolerated under determined circumstances, as well 
as the generally efficacious doses, and give precise rules of 
posology. 

FUNCTIONAL DOSES 

When we desire to correct a functional disturbance we 
naturally employ the smallest dose capable of fulfilling the 



82 PRINCIPLES OF THERAPEUTICS 

indication. To give a larger dose is not only useless, even 
if well tolerated, but harmful, because by stimulating the 
organ to exaggerated activity, it exposes it to consecutive 
miopragia, which is certain in proportion as the resisting 
power of the organ is diminished. The consequence is often 
wrongly attributed to habituation; it is true, however, that 
if small doses had been given, it would be possible later to 
overcome habituation by increasing the amount of the remedy, 
whereas, after large doses, whose action is exhausted, whether 
through miopragia or through habituation, the physician is 
disarmed. 

We should like to note that it is not good practice to seek 
to secure complete functional correction by means of drugs. 
If the organism is placed, through hygiene, under the con- 
ditions of optimum of function, a small dose of medicine often 
suffices to bring about restoration of the disturbed function. 
It is often better to be content with improvement and mod- 
estly live according to appropriate hygiene rather than to 
seek the medicamental triumph of complete functional restor- 
ation which will not last. A patient with mitral stenosis, for 
instance, who knows enough not to ask of his heart more than 
it can give, will have the greatest chances of continuing long 
without the aid of medicinal assistance; and when one is at last 
obliged to resort to digitalis, minute doses, as has been shown 
by Dr. Huchard, are to be prescribed. To content oneself 
with producing diuresis, through theobromin, in a patient 
suffering from renal insufficiency would be a reprehensible 
practice; it is better, first, to restrain all the endogenous and 
exogenous intoxications, and prescribe only small doses of 
the diuretic remedy, which can be repeated whenever necessary. 



DOSES 83 

The patient's mode of life and alimentation should first of all 
be adjusted to their functional forces, while medicinal inter- 
vention should be regarded as a therapeutic adjunct. 

There is a case, however, in which a large dose is demanded 
from the beginning, that is, in the presence of an accident 
immediately menacing life when an active medicament alone 
can restore the adequate function of the failing organ. Such 
is in particular the case in cardiac asthenia capable of endan- 
gering life, or in an alarming dyspnoea, or in sudden anuria, 
in which large functional doses are necessary. There should 
then be no hesitation in seeking energetic action, unless some 
positive contraindication exists. The patient's salvation may 
depend upon such action. 

The variations in functional doses are much wider than 
in specific doses, because the former depend at the same 
time upon the patient's functional needs which are very vari- 
able, and his degree of tolerance which is generally dimin- 
ished. The functional need in cardiopathy may indicate 
doses of digitalin varying from 1/10 mg. to 1 mg.; an intes- 
tinal embarrassment may require doses varying from 5 to 
60 grm. of castor oil, etc. 

The variations in the patients' tolerance are perhaps still 
more numerous. Besides persons who tolerate without in- 
convenience 1 grm. and even more of quinin, there are others 
who cannot take 10 eg. without some phenomena of intoler- 
ance. I shall return to this subject when studying this par- 
ticular disposition. The variations in individual tolerance 
are modified also by disease. A dose that is innocuous in a 
healthy subject may pass from the therapeutic to the toxic 
category if it is given to a sick person : such is antipyrin, which 



84 PRINCIPLES OF THERAPEUTICS 

is generally well borne by apyretic subjects and always dan- 
gerous in the feverish in a state of cardiac asthenia, owing 
to the depression it occasions. In this respect nothing is 
more striking than tuberculin, which is inert in a healthy 
subject, but capable of producing a most violent reaction in 
the tuberculous. The cardio-tonics also may be cited which 
act directly on the heart and which, well tolerated by patients 
with sound hearts, may become very suspicious, even in mod- 
erate doses, in subjects whose hearts are intoxicated. 

This mode of procedure with moderate doses of functional 
medicaments might be judged contradictory at an epoch 
when many physicians are still imbued with the principles 
of physiological therapeutics. It is known, for instance, 
that Potain prescribed digitalin, which is the ideal functional 
remedy, in enormous doses against the cardiac insufficiency 
of asystole. I have no doubt, notwithstanding the high au- 
thority of this master so eminent in cardio-pathology, that 
his manner of administering digitalin (a single dose of 1 mg.) 
is defective. If, in his hands, it has given good results, it 
is because he prepared his patients for digitalin through milk 
diet and rest; furthermore, rest in bed was obligatory while 
the patient was under the influence of the drug. 

Is not this excessive precaution itself the condemnation 
of the method? If so much prudence is necessary, it is be- 
cause the procedure is evidently dangerous. So it certainly 
is, since most of Potain's disciples have abandoned it. While 
preparing the patient, viz., putting heart and kidneys in a 
state of optimum of function through hygiene, it is unneces- 
sary to give such large doses of digitalin to correct the cardio- 
renal insufficiency. Instead of 50 drops of 1:1000 digitalin 



DOSES 85 

solution at once, 20 drops should be given, then 10 drops 
twice a day on each of the two following days; that is 60 drops 
in three days, and the result will be, owing to the cumulat- 
ive action of the drug, a no less notable functional improve- 
ment, and this without danger. I even believe it will prove 
more continuous and lasting. The necessity of large doses 
of functional medicaments cannot therefore be established, 
even in regard to cardiopathies, by Potain's practice, which, 
being alike dangerous and useless, must be renounced. 

SYMPTOMATIC DOSES 

Symptomatic doses are those capable of attenuating or 
removing a symptom without the assistance of a modification 
in the morbid cause or correction in the working of a diseased 
organ. They act by modifying the properties of a tissue or 
the function of an organ without there being any necessary 
relation between this tissue or this function on the one hand, 
and the morbid disturbance on the other. This independ- 
ence differentiates symptomatic therapeutics from func- 
tional therapeutics which acts upon the disturbed function, 
either directly by an action upon the organ whose involve- 
ment causes the disturbance, or indirectly through that part 
of the nervous system which governs this organ, or else through 
an organ in functional connection with the latter. Heroin, 
for instance, in exciting the respiratory center, facilitates 
the breathing of dyspnceic patients, but it may act neither 
upon the cause of dyspnoea, nor upon the organs upon which 
the symptom depends. Likewise, morphin prevents the 
perception of pain through an action on the central nervous 
system (retraction of the protoplasmic prolongations of the 



86 PRINCIPLES OF THERAPEUTICS 

neurons), but its action bears directly neither on the cause 
of pain nor on the suffering organs. 

Symptomatic doses are often almost toxic, since they 
are not efficacious unless given in amounts large enough to 
act in an appreciable manner on the tissues or organs which 
they affect. This is the reason that their variations are not 
very wide. They are quickly limited by the toxic effects 
they produce. Therefore, knowledge of the pharmacody- 
namic effects of symptomatic doses is particularly necessary, 
in order not to exceed therapeutic doses. This remark is 
especially applicable to analgesics, hypnotics, and antither- 
mics, the limits of which between the utilizable physiological 
action and the toxic action are generally narrow and not 
sufficiently precise. It is easy to pass from one to the other 
(cocain, veronal, antipyrin, phenacetin). 

REPARATIVE DOSES 

The reparative medicaments, being in reality aliments 
rather than drugs, their posology has a wider range. All that 
is necessary is to avoid doses capable of giving rise, of them- 
selves, to pharmacodynamic or local harmful effects. It is 
also well to note that the total assimilation of restoratives is 
not to be relied upon. Some part of these is destined to 
elimination, and this elimination is possible only by labor 
imposed upon the eliminating organs. It is, therefore, ra- 
tional not to prescribe these reparative remedies in excessive 
doses, nor for .too long a time. 

Rigor in posology is indispensable not alone in the adminis- 
tration of medicines. It is equally so, and no less imperiously, 
in the distribution of non-medicamental therapeutic meas- 



DOSES 87 

ures (mineral waters, electricity, climatic influences). Here, 
too, in many cases, it is possible to vary the doses as it is desired 
directly to combat disease (phototherapy, radiotherapy, radium 
therapy), or as the purpose is only to modify the function 
(obtaining diuresis through some mineralized water, gastric 
modifications through Vichy waters), to regulate local circu- 
lations (thermal waters, Brides, Bargnoles-de-FOrne, mas- 
sage), or to modify the circulation of the entire cutaneous 
system (carbo-gaseous baths of Royat), or to stimulate the 
nutritive functions, etc., etc. But it is right to recognize 
that the scientific study of the agencies of physiotherapy 
is as yet too little advanced to enable us always to determine 
their appropriate doses with the same certainty as we can 
determine those of most medicines; not infrequently this 
posology is purely empirical. 



CHAPTER V 
MEDICINAL OPPORTUNITY. 

Importance of previous conditions of hygiene — Reasons for the employ- 
ment of medicines and for the doses to prescribe — Duration of medicinal 
prescription — Alternation of medicines — Polypharmacy and oligopharmacy. 

IMPORTANCE OF PREVIOUS CONDITIONS OF HYGIENE 

It is not without anxiety that a conscientious and educated 
physician begins medical practice, namely, therapeutics. 
Usage demands that he should have studied everything 
except what is most important to know: how to institute a 
treatment. For a long time he is troubled by the question: 
What medicine shall I prescribe? This anxiety is twofold: 
it exists, and it must not be noticeable. Patients are sus- 
picious. If they sometimes readily accept, or even praise the 
meditations of an old practitioner, they watch the young physi- 
cian and do not excuse him for any hesitation in prescribing, 
thus confounding knowledge and assurance, ignorance and 
scruple. Hence he is obliged to conceal his meditations and 
misgivings. The fact is that the medical practice cannot dis- 
pense with diplomacy any more than any other profession, 
even in the interest of the patients themselves. Is it pos- 
sible, for instance, not to consider the fondness of some and 
the repugnance of others for medicine? It is sometimes as 
difficult to convince the former that they can get well with- 
out medicine as it is to persuade the latter to accept 
the necessary medicine. The art of persuasion naturally 

intervenes. 

88 



MEDICINAL OPPORTUNITY 89 

In order to spare himself all unnecessary embarrassment, 
the physician must adopt a guiding principle, that is, to con- 
sider the medicinal prescription as the last thing to be attended 
to, and to give his attention first to the complete interrogation 
and examination of the patient. He will thus be able to 
institute a rational therapeutics according to the diagnosis 
and pathological physiology deduced from observation. This 
solid basis of therapeutics is too often inadequately prepared 
either because examination is restricted to the organ to which 
the patient has called attention, or because, owing to haste, 
material difficulty, or overconfidence in an apparent benignity, 
no thorough examination is believed to be necessary. It is 
owing to this lack of thoroughness that the physician fails 
to recognize a pleural effusion, permits tuberculosis to become 
established, or an incipient diabetes, infection of the intes- 
tines, renal or hepatic insufficiency, to attain serious degrees 
of development. However benign the appearance of a morbid 
state, the therapeutist must acquaint himself with the func- 
tional activity of the entire organism, including the amount of 
the urine and of abnormal products, the state of sensibility, 
spasm, or relaxation of the large intestine, sleep, the hepatic 
function, etc., etc., and in the case of women, the menstrual 
function. A woman will resent a thorough examination of 
her utero-ovarian conditions when it is unnecessary, but she 
will not excuse the physician if he should neglect to make 
adequate inquiry in this respect. The patient's habits and 
mode of life should also be taken into account. 

The next care of the physician must be to place his patient, 
as soon as possible, in a condition of optimum of functioning 
and of the greatest possible comfort. We often see the eon- 



90 PRINCIPLES OF THERAPEUTICS 

dition of a feverish patient improved in a few hours owing 
to the mere fact that he has been isolated with his nurse in 
very large, well-ventilated rooms at an appropriate tem- 
perature, and complete rest, proper diet, with plenty of drink, 
and rigorous cleanness, both personal and environmental 
(washing of mouth, teeth, nose, hands, face, etc.) has been 
secured for him. And all this, of course, done in a manner 
not to cause any fatigue. Such thorough hygiene, enforced 
from the first in a case of infectious disease, may exert a 
decisive influence upon the progress. 

Then only, that is, after the thorough examination and the 
prescriptions of a hygienic character, will the physician think 
of drugs. Except in cases of urgency and of specific treat- 
ment, he can always, especially at the beginning of an attack, 
take his time to think or even study for the prescription of 
important medicines, and to confine himself to some harm- 
less prescription (a few centigrams of quinin, sometimes a 
very light laxative, for instance). Not infrequently the 
patient will in the meantime recover from benign though 
tumultuous infections (influenza, tonsillitis, indigestion, slight 
enteritis) which behave like fire in straw. A physician who 
has sometimes been a witness of such favorable evolution 
will avoid precocious medicinal overcharge. On the other 
hand, how many patients, in less than twenty-four hours 
after the invasion of such slight infections, have already been 
submitted to purgatives, enemas, revulsives, antipyretics, 
antiseptics, and what not, who would have spontaneously 
recovered within a day or two with nothing but rest, tran- 
quility, and diet. 



MEDICINAL OPPORTUNITY 91 



MEDICINES AND DOSES PRESCRIBED 

No difficulty will generally be experienced in the employ- 
ment of specific medicines and remedies which are best known, 
best regulated and most easily administered. There are 
cases of this order which demand urgent action, even when 
there is some doubt, provided the 'probabilities are on your 
side; for instance, in the case of an angina suspected to be 
diphtheritic in character. It is hardly necessary to say that, 
in these cases, one should resort immediately to laboratory 
measures of certainty in order rigorously to determine the 
line of conduct to be pursued. 

The serious difficulties begin with functional and symp- 
tomatic therapeutics. An anomaly in the function of an 
organ does not forcibly necessitate medicinal interference; 
it must first be carefully analyzed and appreciated in the 
light of nosology, prognosis, and pathological physiology. 
If it is of little importance and transitory or of a benign prog- 
nosis, if it is not associated with any trouble in the sufficiency 
of the function upon which it depends, if it is well tolerated, 
it requires no more than the simplest hygienic measures. In 
other instances, the anomaly is very pronounced, but nosology 
teaches that it is without gravity. In still other cases it 
demands interference corresponding to its origin, importance, 
functional derangement which it expresses and the means 
that are at our disposal. 

Let us study one of the most frequent cases of anomaly in 
the external manifestation of a function: acceleration of the 
pulse. It may be due to most varied causes and have a very 



92 PRINCIPLES OF THERAPEUTICS 

variable significance. Should it arise from sudden emotion, 
or too violent muscular movement, it may be overlooked. 
Should it accompany digestive derangements or neurasthenia, 
it would require no special treatment and would be modified 
with the conditions upon which it depends. Should it assume 
alarming proportions as, for instance, intermittent tachy- 
cardia of neurasthenics, it would demand special treatment; 
in most cases, however, rest in bed, warming the limbs, and 
especially the soothing effect of the formal assurance that 
the incident is devoid of gravity and that it will readily vanish 
without any lasting trouble, would suffice to bring about con- 
siderable sedation. In graver forms a more complicated treat- 
ment and one of more uncertain results should intervene. If 
the acceleration of the pulse is connected with a disease in 
the course of which it is observed as a symptom, it demands 
no other treatment than that of the disease itself: such is 
the case in Basedow's disease. 

In other instances acceleration of the pulse is due to a state 
over which we can have but little power: a cachexia, for ex- 
ample, or compression of the pneumogastric by tuberculous 
ganglia. 

We may well endeavor to combat the cachexia or treat 
the ganglionic tuberculosis, but we shall be able to do very 
little against the anomalous frequency of the pulse, which is 
to be reduced to a minimum through rest. 

In the foregoing instances the anomalous frequency of the 
heart beat constitutes in itself only a very limited indication 
for medicinal interference, and that mostly in relation to the 
disease upon which it depends. In fact, the irregularity and 
quickness of heart action that causes no disorder in the 



MEDICINAL OPPORTUNITY 93 

circulation does not necessitate active treatment except 
when the disorders are excessive or prolonged or render prog- 
nosis unfavorable. 

This same anomaly, acceleration of the pulse, will now fur- 
nish us with an illustration of the main eventualities in which 
it may be attended by functional insufficiency to be combated 
with some chance of success. 

In pulmonary tuberculosis acceleration of the heart is a 
bad symptom: it generally accompanies the grave and rapid 
forms. Conversely, tuberculous subjects with a slow pulse 
present slow forms tending to recovery. Moreover, this 
anomaly already constitutes a functional disorder, since it is 
attended by perturbations in the arterial pressure which is 
generally lowered. The problem arising from these observa- 
tions is undoubtedly complex, and it may be asked whether 
acceleration of the pulse and decrease of blood pressure pro- 
ceed exclusively from a special toxicity of tuberculosis or 
from a predisposition on the part of the subject; neverthe- 
less, this anomaly being, as it is, both a sign and a factor 
of gravity, it is legitimate to attempt to correct it as far 
as possible, while an effort is also made to avoid increased 
pressure. In the beginning, rest in the recumbent position, 
regularity of meals, and sometimes reduction of the fever 
will combine to this end. In some cases strychnin is small 
doses, at times digitalis, will prove useful adjuncts. 

These measures, although rational, often fail in the begin- 
ning of the disease and always in its advanced stages, which 
proves that functional therapeutics does not cure. It may 
assist the organism when the latter is at the mercy of a func- 
tional disorder and is defending itself, but it is almost cer- 



94 



PRINCIPLES OF THERAPEUTICS 



tainly destined to failure when the organism is profoundly 
affected. We shall now find this therapeutics all-powerful 
in a case in which functional insufficiency is the principal 
morbid element. 

Here are two persons who manifest, together with an accel- 
erated pulse, the signs of a lesion at the mitral orifice: in one 
there are also found the usual symptoms of cardiac insuffi- 
ciency (dyspnoea, cough, oedema, oliguria, insomnia, etc.); 
in the other, in spite of the orificial lesion and the frequency 
of the pulse, one would in vain look for the slightest sign of 
circulatory disorder; it is noticed, however, that the subject 
is young and impressionable. In the former case patholog- 
ical physiology will enable us to recognize the quick pulse 
as the result of weakness of the heart which empties itself 
incompletely at each systole, and which therefore is incited 
to contract more frequently in order thus to compensate the 
insufficiency of contraction. In the second case the acceler- 
ation of the heart beats is to be regarded as the result of 
simple nervous overexcitability of the heart. Thus we see 
that the same phenomenon in two subjects suffering from the 
same affection indicates a different therapeutics. 

In the first case, we should resort to the corrector par 
excellence of cardiac insufficiency of organic origin — digitalis — 
which is one of the most remarkable agents of functional 
therapeutics: within a very short time, if the disease is not 
too far advanced, we shall see diuresis re-established, the 
oedema dissipated, the pulmonary circulation regulated, 
the pulse-rate lowered and regulated. In the second case, we 
should confine our endeavors to the palliation of the symptom 
through rest, assisted sometimes by Valeriana or a bromid. 



MEDICINAL OPPORTUNITY 95 

And if digitalis is given in very small doses to reduce the pulse- 
rate (which is sometimes indicated), it is no longer as a func- 
tional but as a symptomatic treatment, in the special and 
abstract case we have supposed. 

But this same marvelous functional medicine, digitalis, 
must be avoided in other cases of accelerated pulse, even when 
attended by cardiac insufficiency: such is the case in a patient 
suffering from typhoid, and presenting a heart beating 130 
times to the minute. This example presents one of the most 
difficult problems of therapeutics. 

The pulse is relatively slow in regular typhoid fever and 
seldom exceeds 100 pulsations to the minute. Should it ex- 
ceed 110 and especially 120, we must be on our guard. With 
certain nervous subjects whose pulse is habitually rapid, such, 
particularly, as young girls, this acceleration may be devoid 
of any necessarily bad significance, especially if the situation 
is otherwise fair and if the rhythm of heart sounds is normal; 
it then requires no more than a more watchful solicitude, 
and precautions for rendering the impressions of bathing 
gentler. But if the frequency of the pulse should occur in 
the course of the disease in an average subject, and especially 
if the other symptoms should grow worse, then a pulse of 
130 is rightly to be considered as a phenomenon of great 
gravity. 

Ideal therapeutics would then consist in first accurately 
determining the pathogenesis of the anomaly, which may 
depend upon intoxication of the myocardium or of its nerves, 
upon myocarditis, or perhaps upon hypophyseal insufficiency, 1 
and, next, in employing such therapeutic agents whose mode 

1 We naturally exclude cardiac acceleration due to perforative peritonitis. 



96 PRINCIPLES OF THERAPEUTICS 

of action, accurately known, is adequate to the needs. But 
such mathematically accurate interference is not always 
possible, and yet quick action is required in order to avoid 
the risk of seeing the patient succumb. Without pretend- 
ing to fix rules for such a delicate case, I should like to state 
how, personally, I would consider the solution of the problem. 

If the patient with cardiac acceleration presented no marked 
modification in the normal relations of the heart sounds and 
silences, I would conclude that the phenomenon was due 
to intoxication of the heart and of its nerves. I would nat- 
urally make reservations as to the possibility of hypophys- 
eal insufficiency. It is certain that in the presence of the 
so-called hypophysial syndrome, which is characterized by 
diminished arterial tension, acceleration of the pulse, and 
decrease in the quantity of urine, we must think whether 
the case is one of insufficient activity of the hypophysis, and 
resort to hypophyseal opotherapy. But this question being 
still under study, we cannot confine ourselves to this attempt. 
Besides, the diminished activity of the hypophysis prob- 
ably results from typhoid intoxication and, whether it be 
the myocardium, the nerves or the hypophysis that we have 
to disinfect, the therapeutic procedure would vary but little. 
It should consist in stimulating diuresis to a minimum of 
2 liters (quarts) in a woman and from 250 to 500 grm. more 
in a man. The best means of securing this result is the com- 
bination of a water diet, cold bathing, and cold applications. 

In order to obtain the full results of a water diet, the milk 
ration should be reduced to a maximum of one liter (1,000 
grm.) and the quantity of water raised as much as possible, 
the water being taken cold and in small amounts, but at fre- 



MEDICINAL OPPORTUNITY 97 

quent intervals, so as to obviate accumulation of liquid in 
the stomach. It is possible to introduce some of it into the 
system by means of enemas and through the subcutaneous 
cellular tissue, especially if the arterial tension is reduced 
(physiological salt solution in small quantities so as to give 
rise to no strong reaction). 

Cold bathing is not at all free from danger for typhoid 
patients with weakened hearts; it is, therefore, well to 
prescribe, thirty minutes before the bath, 1/2 or 1 eg. 
of sulphate of spartein whenever the number of heart 
beats exceeds 115 to the minute. Moreover, the patient 
must be spared the shock of cold, and, to this end, bathing 
should begin with a temperature not below 33° or 34° C, 
according to the susceptibility of each patient; and the water 
should be cooled progressively to the degree necessary to 
increase diuresis. In such cases I would personally and 
carefully watch the effects of cold resulting from the bathing 
upon the heart and circulation, and would not insist on this 
measure should I observe, under its influence, the slightest 
disturbance in the heart's action. In fact, nothing is easier 
than to supplement the action of these incomplete and insuf- 
ficient baths by keeping an ice-bag on the head, by frequently 
renewing cold compresses over the abdomen or even replac- 
ing them by an ice-bag, giving enemas more frequently, re- 
sorting, at need, to cold affusions containing aromatic vinegar, 
and finally adding to these measures an ice application to 
the precordial region, according to the method advocated by 
Dr. Leduc, and following the usual technic, the details of 
which I cannot discuss here. 

If hypophyseal therapeutics could render the same service 
7 



98 PRINCIPLES OF THERAPEUTICS 

as does this delicate and complicated medication, it would 
undoubtedly mark a notable progress in therapeutics of ty- 
phoid fever. 

If in addition to cardiac acceleration I should observe the 
approach and identification of the sounds and silences of the 
heart (embryocardia), I would diagnosticate an infectious 
myocarditis and modify my treatment accordingly. I do 
not forget that the ideas thus far admitted in regard to infec- 
tious myocarditis are subject to revision, but that has no im- 
portant bearing on the therapeutics. For the latter it is 
sufficient to know that the symptom embryocardia corresponds 
to the most dangerous stage and the gravest prognosis of cardiac 
asthenia, as well as to the most unfortunate susceptibility of the 
heart. Under these conditions the patient must be kept at 
rest and spared brutal effects, which necessitate omission of 
bathing. Cooling may be obtained through rigorous applica- 
tion of the means already referred to. While diuresis is pro- 
moted by them, the water diet, with the aid of a moderate 
quantity of milk, furnishes the needed water. Moreover, I 
believe that instead of spartein, which is inadequate, the 
extract of strophanthus (which appears to be the true remedy 
for myocarditis) should be given in milligram doses, to be 
repeated once or even twice in twenty-four hours if there is no 
improvement. Lastly, I would not neglect to give at the 
same time three or four 10-cg. cachets of the entire powder 
of bovine hypophysis. 

As to digitalis, I should consider its use clearly contrain- 
dicated in both these cases, because its too direct action on 
the heart would be added to that of the typhoid poison, and 
it appears to me dangerous to overcharge with the action of 



MEDICINAL OPPORTUNITY 99 

an active and toxic medicine, an organ already imperiled by a 
morbid influence. Organic and functional therapeutics works 
better when practised through intermediaries. This is the 
reason that spartein, which has no action on the cardiac fiber, 
is the true medicine for intoxications of the myocardium, 
whatever their origin may be. It may, however, prove to 
be inadequate. Then only would I resort to small doses of 
strophanthus. 

A last illustration of acceleration of the pulse in another 
infection will furnish a precept diametrically opposite, i.e., 
that of expectation pure and simple. In a subject, especially 
a child, suffering from scarlatina, a pulse of 130 to the minute 
is not alarming. Nosography teaches us that this anomaly 
is transient and is of no unfavorable significance by itself, if 
otherwise the evolution of the disease is regular. No treatment 
other than that commonly employed in scarlatina should 
therefore intervene so long as the evolution of the disease 
remains regular. 

In brief, an anomaly offers only a secondary importance in 
itself when it is well tolerated. It assumes importance only 
by virtue of its intensity, duration, meaning, prognosis, and 
by the functional disturbances and lesions associated with it. 
It is by these various elements that medicinal intervention 
is actuated. This intervention will be functional if the design 
is to correct an actual or anticipated functional trouble, or 
to support a function hampered by a lesion, or to combat 
intoxication. It will be symptomatic if we desire to moderate 
the intensity or shorten the duration of the anomaly. 

Functional restoration does not give as brilliant success as 
specific therapeutics. In most cases the entourage of a sick 



100 PRINCIPLES OF THERAPEUTICS 

person does not realize the amount of knowledge, attention, 
and perspicacity called into play on the part of the physician 
in interpreting a morbid phenomenon (whose gravity he usually 
does not reveal in order not to alarm the patient or those to 
whom he is dear), and in combating it through the appropriate 
corrective. But the true therapeutist, who is well aware of 
the effort exerted and of the result obtained, will sometimes 
experience the same joy of conscience that a surgeon does 
after an operation performed in time to save the life of a 
patient. 

Such are the difficulties and complexities of medicinal 
intervention when we wish to practise rational therapeutics, 
but it is readily conceivable that in this duel between disease 
and physician, the latter, who generally has under observation 
a slow development following a course well-nigh foreseen, 
may take time for observation, reflection, and study. Such 
is not the case, however, with symptomatic therapeutics. 
Here, abstention is more delicate because, besides the vital 
indication which urgently demands intervention, the patient 
wishes to be relieved as soon as possible. In fact, as soon as 
a patient has placed himself in the hands of a physician he 
no longer regards his disease, but the physician responsible for 
his suffering. If he continues to suffer it is because the doctor 
has failed to relieve him, and whatever may subsequently 
happen, it is the prescribed medicine that is accountable for 
it; and even when, owing to the progress of the disease, the 
sensations of the patient change, he is tempted to attribute 
these modifications to the measures of treatment. 

Moreover, the medication of symptoms is the only one 
understood by laymen. When sending for a physician they 



MEDICINAL OPPORTUNITY 101 

not infrequently formulate the medication in advance (they 
want a morphin injection, for instance). Others welcome the 
physician by asking him to "cut" their fever. Mothers of 
families who are more or less affiliated with societies for first 
aid to the injured in the army nowadays venture to treat per- 
sons of their acquaintance by active medicines. In the belief 
that they are doing a good service and having no idea of the 
dangers to which they expose people, they willingly distribute 
quinin, antipyrin, purgatives, gargles, etc. In these cases 
it is symptomatic therapeutics, the least important, but not 
the least dangerous, that is practised. If the infection is 
short and benign, the patient recovers. If it is grave, the 
physician is called in and finds himself in the presence of a 
patient who has been drugged but by no means treated. 
Therefore, from all points of view, it is necessary carefully to 
study symptomatic therapeutics. 

In this mode of therapeutics the medicinal opportunity 
always results from excess of the morbid disturbance and 
its immediate dangers for the patient's life. In the absence 
of these conditions it is not absolute. 

To illustrate this I should say it is bad practice (contrary 
to what is read almost everywhere) to employ morphin in 
hepatic colic; but should the pain, in spite of employment 
of means commonly more efficacious, torture the patient 
too much by its intensity and persistence, there should be 
no hesitation to resort to it. Does not the same procedure 
often impose itself in regard to cases of severe and extensive 
burns? And yet is there any disease in which the integrity 
of diuresis is more necessary? Hypnotics should, of course, 
be avoided, and an effort made to modify the course of in- 



102 PRINCIPLES OF THERAPEUTICS 

somnia by hygiene, but if this fails and the insomnia is acci- 
dental, is it rot better to prescribe a medicine of this order 
rather than to allow the patient to pass long, sleepless nights, 
liable to intensify his nervous exhaustion? The majority 
of antithermics are to be regarded with suspicion. But if 
there are no other means for lowering an excessive and con- 
tinuous temperature, it is preferable to resort to such a remedy 
than to permit the patient to become exhausted by the fever 
and its consequences (anorexia, weakening of the heart, etc.), 
provided, of course, this is done with prudence and judicious 
selection of the medicinal agency, especially if the heart is 
weakened, and in this case failure is prevented by adminis- 
tering at the same time small doses of a cardiac stimulant, 
such as spartein or even caffein. 

It is never, wise to give to a feverish subject at the acme 
of the fever large doses of antithermics, especially antipyrin. 
This rule is still more absolute if the heart is depressed; this 
last circumstance demanding that even small doses be re- 
garded with distrust and be combined with some cardiac 
stimulant. In benign infections antipyrin sometimes pro- 
longs the disease. For the sake of illustration, let us take 
two patients, both having weak bowels or kidneys, both at- 
tacked by either indigestion or influenza. One of them takes 
a good dose of antipyrin, the other takes nothing or only 
minute doses of quinin. The illness of the former will cer- 
tainly be more prolonged than that of the latter, and he will 
suffer from oliguria and exaggeration of toxic manifestations. 
The physician must therefore observe the delicate features of 
symptomatic therapeutics if he wishes at once to safeguard 
the interests of the patient and his own authority. A con- 



MEDICINAL OPPORTUNITY 103 

scientious and learned physician, who sees farther than the 
symptom, will do well to explain his conduct when he does 
not combat a symptom. By virtue of his solicitude for 
the patient and his knowledge of nosography which enables 
him to foresee the prognosis, he can persuade his patient to 
accept the probable evolution of the disease. He will gener- 
ally (not always!) have the satisfaction of being understood 
and be able to palliate only the most marked symptoms, 
while watching the functional disturbances in order to correct 
them at the opportune moment, and lead the patient to 
recovery. 

On the other hand, the physician should not systematically 
refuse a symptomatic measure. A patient who has already 
profited, or believes he has profited, by the soothing of a 
symptom through a certain treatment, should not be deprived 
of the same treatment unless there be good reasons for hoping 
for better treatment or else fear of some inconvenience. In 
this respect there is a general rule. As it is always well to 
let patients speak, even when they speak a great deal, because 
by speaking they give themselves up and by listening to them 
we study them and know them better, so it is well, in thera- 
peutics, to be informed by them and take into account their 
experience of the medicines, without, however, overlooking 
the possibilities of autosuggestion. This is particularly true 
as regards the employment of purgatives, sedatives, and 
hypnotics. It is also wise to consider the mentality of certain 
persons and not to insist upon correcting their errors. What 
is the use of fatiguing a patient by unprofitable discussions? 
Is it not more sensible to give him the satisfaction of an infini- 
tesimal dose, incapable of any harm, and let him profit by 



104 PRINCIPLES OF THERAPEUTICS 

the nervous dynamism which the joy of hope and assurance 
is capable of arousing? 

I do not think it necessary for me again to refer to the 
drawbacks of symptomatic therapeutics and to the dangers 
of employing it exclusively as I am sure there is not a single 
physician who would confine himself to combating exclusively 
the symptoms of a disease. One could easily work miracles 
by morphin, chloral, and antipyrin if these miracles did not 
present the formidable reverse of not curing at all, and some- 
times aggravating disease or even killing the patient. 

The medicinal opportunity in reparative therapeutics is 
more easily determined and less risky, because a reparative 
medicine is in reality nothing else than an aliment. It plays 
merely the part of an adjunct in the treatment which con- 
sists, first of all, in a combination of hygienic measures, whose 
essential feature is diet. The patient will obtain the recon- 
structive elements which he needs from the special alimen- 
tation prescribed for him and, by a suitable mode of life, 
will avoid useless expenditure of force. Therefore, if the 
medicine is efficacious, so much the better; if not, there will 
be no peremptory clinical reason to know it. It is also for 
similar reasons that mineral phosphates have for many years 
been praised as restoratives and then abandoned, giving way 
to phospho-glycerates which received the same praises and 
arguments, and the latter have given way to organic phos- 
phates, whose value is rendered more probable by studies of 
biological chemistry and physiology, but some of which, as 
lecithin, are already being left behind. And this has been 
going on without any inconvenience to either patients or 
physicians. 



MEDICINAL OPPORTUNITY 105 

An exception is to be made in favor of iron which has de- 
served the name specific for chlorosis. It is perhaps not 
a mere restorative and has an important pharmacodynamic 
action. At any rate, it is at times difficult to do without it. 

We must not think, however, that reparative medicines 
can be prescribed without inconvenience on the pretext that 
they are a kind of food. As has already been stated, their 
employment is restricted by the pharmacodynamic action 
of some of them and by their lack of utilization. For instance, 
soluble phosphates, whether mineral or organic, exert upon 
the nervous system of certain patients an excitation which 
must be taken into account, especially if it is attended by 
palpitation; cod-liver oil, when taken in large doses may give 
rise to diarrhea; iron to constipation, malaise, an uncomfort- 
able sensation of fullness, vesical irritation, etc. On the other 
hand, if a part of medicinal phosphates, instead of being assim- 
ilated, is simply eliminated through the urine, it is quite use- 
less to fatigue the kidneys in this work. Therefore, even 
when dealing with substances that are integral parts of the 
organism, tolerance has a limit not to be trespassed upon 
with impunity. Another evidence of this fact is sodium 
chlorid which, in doses relatively not very large, is toxic and 
may prove fatal. The truth is that in therapeutics nothing 
is commonplace. 

The question of dose is related to that of medicinal oppor- 
tunity. As the action of doses has already been discussed in 
a special chapter, we shall confine our remarks to a few points 
of particular importance. * 

1. There is no necessary relation between the so-called 
physiological, in fact toxic, effects and the curative effects 



106 PRINCIPLES OF THERAPEUTICS 

of a medicine. Thus, curative remedies cure by direct or 
indirect, etiocratic or specific action upon disease. The others 
can do no more than help or soothe. There is no reason, 
therefore, by prescribing large doses, to seek the production 
of physiologically marked effects for the purpose of curing. 

2. Specific and etiocratic medicines cure in doses which 
must not, as far as possible, be attended by any undesirable 
physiological effects. If any effect of this kind is produced, 
it is accepted; but there is no reason whatever for seeking to 
produce such effects (iodids, mercury, salicylate of soda. etc.). 

3. Functional medicines are capable of correcting impor- 
tant functional disorders in doses which, except for their se- 
lective properties, should, as far as possible, be unattended by 
any notable action upon the rest of the organism (theobromin, 
digitalin, spartein, antimony, purgatives) ; they are sometimes 
active even in almost infinitesimal doses (nux vomica, mi- 
nute doses of digitalin, spartein, 1 etc.). 

-i. As a rule, there is advantage in dividing the doses of 
functional medicines. We thus obtain a more lasting action, 
obviate too lively impressions, and are sure never greatly to 
exceed the tolerated dose, whatever the idiosyncrasy of the 
patient. 

5. Functional doses should be the smaller in proportion as 
the organs to be acted upon are more imperilled; and, when- 
ever possible, we must avoid heaping upon the same organ a 
medicinal and a toxic action of morbid origin. For this pur- 

*It will be readily recognized that 1 eg. (and even less) of sulphate 
of spartein, for instance, produces effects quite adequate for a dose, which 
may of course be repeated; it is therefore useless to give 5 eg. in one dose, 
as is usually done. Likewise, saline laxatives, in spite of a long-standing 
error, can produce laxative effects in doses of 6 or 7 grm. The same re- 
mark holds good for many other medicines. 



MEDICINAL OPPORTUNITY 107 

pose, when we have to strengthen an organ weakened by 
the influence of intoxication bearing upon this organ, we 
must strive indirectly to act upon it either through the ner- 
vous system or through some other sound organ. Thus, an 
intoxicated myocardium may be stimulated through the ner- 
vous system by means of spartein without exercising any 
direct action upon the myocardium itself. The needs of 
renal depuration may be limited by the diet and by depura- 
tive action upon the digestive tract. We have already given 
a number of examples of this indirect mode of action upon 
a disturbed function. 

G. As symptomatic medicines are, as a rule, to manifest 
their action only upon the symptom for which they are pre- 
scribed, the doses should be limited strictly to the produc- 
tion of the desired effect. 

7. Reparative medicines may be prescribed in large doses, 
provided they produce no bad pharmacodynamic effect and 
that they be utilized, i.e., do not fatigue the emunctories in 
useless elimination of the excess prescribed. 

To sum up, except specific medicines which, as a rule, re- 
quire fairly large doses, there is, in the immense majority of 
cases, advantage only in prescribing small doses, that is, 
doses considerably smaller than those usually recommended 
by formularies and treatises on therapeutics. 

DURATION OF MEDICINAL PRESCRIPTIONS 

The medicinal opportunity raises a last question: how 
long should the employment of a remedy be kept up? As 
a rule, a medicine should not be administered for too long 
a period of time in order to obviate accumulation which leads 



108 PRINCIPLES OF THERAPEUTICS 

to intolerance, at times even to chronic intoxication or habitu- 
ation. Therefore, when it is necessary to prescribe a medi- 
cine, such as mercury and quinin for a protracted period, 
the action should be interrupted and resumed after a period 
of rest. 

In this regard it is difficult to formulate precise general 
rules; the length of time for which a medicine is to be pre- 
scribed varies with its effects. In the case of specific reme- 
dies, such as antitoxin (antidiphtheritic) and antiparasitics, 
which cure at once, there is no reason whatever for prolong- 
ing their employment. On the other hand, if the medicine, 
even a specific, overcomes only the disorders and leaves the 
disease germs to persist in the economy, as does mercury 
in regard to syphilis, there is enforced obligation to keep the 
organism under the influence of the medicinal impregnation 
as long as this is necessary to obviate the offensive return 
of the pathogenic agent. 

Functional therapeutics, of delicate management under all 
circumstances, finds another difficulty in the question as to 
how long the medicinal action is to be kept up. In func- 
tional therapeutics the medicinal action should, as a rule, 
be of short duration, because as soon as functional restora- 
tion is secured, the medicine becomes useless. By further 
prolonging its action the risk is run of giving rise to the bad 
effects of accumulation and habituation, and especially to 
exhaustion of the organ which would be compelled to work 
above its strength and would, at any rate, be superfluous. 
This is the reason that has led to the practice of a single dose 
of digitalin in asystole. This reaction against the continued 
dose, which formerly was so frequently prescribed, is obviously 



MEDICINAL OPPORTUNITY 109 

exaggerated: rational therapeutics demands restoration of 
the cardio-renal functions without danger, and to this end 
it is perfectly right to divide the dose of digitalin, as has al- 
ready been indicated. 

The dose of a symptomatic medicine is necessarily restricted 
to the removal of the symptom; it seldom intervenes prevent- 
ively nor is its action prolonged. However, some hypnotics 
obey this double condition: they are mostly prescribed pre- 
ventively, and some (sulphonal, veronal, trional) continue 
their action the day following, and sometimes for more than 
twenty-four hours after ingestion. It is all the more impor- 
tant to start with small doses as the symptom generally 
re-appears when the action of the medicine is exhausted 
(pain, fever, insomnia). Hence, one is often led to renew it, 
at the risk of bringing about the serious results of accumu- 
lation and intolerance, or chronic intoxication and assuetude. 
A good way to avoid these results is the alternation of medi- 
cines to which reference will again be made. 

ALTERNATION OF MEDICINES 

The agents of reparative therapeutics are not, as a rule, 
subject to these objections. If they are given to excess, the 
organism eliminates without assimilating them (iron, phos- 
phates, chlorids). It is, however, better not to subject the 
organs to the fatigue of eliminating the non-assimilated part, 
which is easily done by not prescribing too large doses and 
by alternating the reparative medicine with another of the 
same category or one acting to a similar end. We may thus 
alternate with profit organic phosphates with iron, organic 



110 PRINCIPLES OF THERAPEUTICS 

phosphates or iron with arsenic, one of these with strychnin 
or nux vomica when they have a beneficial action upon the 
digestive organs, or with cinchona. 

This alternation of medicines is more than a preventive 
practice calculated to obviate the dangers of accumulation 
or habituation. It has, further, the advantage of the bene- 
ficial change of remedy. In fact, it is a general rule that the 
employment of a new remedy or the application of a dressing 
or a local agent of a different nature from the preceding is 
favorable to the patient. This circumstance should therefore 
be taken advantage of, by alternating the indicated remedies 
which, at each renewal, exert a more favorable influence. 

Furthermore, most medicines give rise in time to some 
inconvenience to the organs receiving or eliminating them, 
or being acted upon by them. It is, therefore, necessary to 
give these organs a timely rest. This also is secured by 
alternation. During the action of a medicine, the organs 
more or less affected by another enjoy rest. A striking illus- 
tration of the usefulness of this practice is furnished by laxa- 
tives. Some, in addition to their action upon the bowels, are 
irritants to the stomach (the majority of laxatives acting in 
small doses in pill form, such as podophyllin, cascara, etc.); 
others depress the gastric function (sulphate of soda); still 
others induce an abundant biliary secretion (podophyllin); 
while some do no more than stimulate the intestinal con- 
tractions, or favor mechanically the movement of the fecal 
matter. Nothing is easier, therefore, than to respect the 
stomach, liver, intestines, by exercising upon them an action 
of only short duration, whenever necessary, by means of lax- 
atives alternated. 



MEDICINAL OPPORTUNITY 111 

This chapter on the opportunity, doses, and alternation of 
medicines includes almost the whole of therapeutic practice, 
but in order to develop it with greater accuracy, it would be 
necessary to review each medicine and its applications to each 
particular case. If I entered upon details of application I 
would give those of my personal practice which has no pre- 
tention to dogmatic absolutism. 

At this point, however, therapeutics is no longer a mere 
science, it is at the same time an art. No doubt this art would 
be absolutely without value if it had not for its basis a solid 
science. It is no less certain, on the other hand, that the 
science would not be sufficient, since the value of the precepts 
of practice depends upon the manner in which they are car- 
ried out. Each physician brings to applied therapeutics his 
own manner, his preferences, his conscience, his education, 
his observing and reasoning mind, in a word the development 
of his personality, while the patient complicates the problem 
by his individual reactions. These details cannot be codified. 

They are suggested to the mind by a habit which is mostly 
derived from medical education. For this reason the teaching 
of medicine should be at least as much educational as instructive. 
It is always easy with time and labor, to develop one's instruc- 
tion; it is not as easy to perfect one's senses, to think medi- 
cally, and do everything with accuracy." To cite a simple 
illustration, there are twenty wrong methods of giving a hypo- 
dermic injection; there is but one good method, which is to 
be acquired and understood by those alone who have the advan- 
tages of a good medical education. The others may be wrong 
all their lifetime without being aware of it if they do not feel 
the need of improvement. It is for these reasons that the 



112 PRINCIPLES OF THERAPEUTICS 

precepts of details cannot be imparted and learned except 
at the bedside, in the presence of patients. 

Medical education being a condition of good therapeutics, 
it is not foreign to our subject to call attention to the only- 
practical way of giving it. It is necessary that each student 
of medicine serve as an externe for one year, and as interne 
for one year (two years if possible) in one of the great hospitals 
of the city where the faculty is situated.. These services 
should be made as accessible to all as possible. Through such 
constant and prolonged contact with patients, at a receptive 
age, the practical side of the personality of the physician will 
be developed, and scientific knowledge and a perfected sense 
of the medical art will be combined in him. 

POLYPHARMACY AND OLIGOPHARMACY 

The question of medicinal opportunity includes that of 
'polypharmacy 'or prescription of numerous medicines either 
simultaneously (complex formulae) or successively. I shall 
be very brief on this subject, contenting myself with the re- 
mark that it renders therapeutic observation impossible, 
since each superadded medicine complicates the pathological 
physiology of the patient; bes'des, it is very d fficult, as it 
associates substances which may modify each other or modify 
their respective effects; and, finally, there are thus imposed 
upon the diseased organism numerous foreign substances 
all the actions of which are not a' ways accurately known. 
One thus runs the danger of doing harm without knowing 
and without being able to understand it. All good thera- 
peutists, particularly Forget, Fonssagrives, have protested 
against polypharmacy. It is well to add that polypharmacy 



MEDICINAL OPPORTUNITY 113 

is generally practised by those who are ignorant of the spon- 
taneous evolution of diseases, or by those who believe they 
are able to modify at pleasure this evolution, or still by the 
zealots of symptomatic therapeutics. As a physician ad- 
vances in practice, he perceives that it is in no way necessary 
to encumber the organism with medicines, that the devel- 
opment of disease is not at all favorably modified by them, 
that symptomatic correction is not always useful, that it is 
at times even harmful. He is thus gradually brought to 
moderate his medicinal prescriptions and simplify his formulae. 
In contradistinction to polypharmacy the name oligo- 
pharmacy is given to the therapeutics of those who think 
they are able to fulfil all the indications with a very small 
number of medicines, six, ten, or twenty at most. Every- 
thing considered, I would rather be treated by a physician 
who knows only a few medicines, but who makes a correct 
use of them, than by one imbued with polypharmacy. But 
why confine oneself to the utilization of twenty medicines 
if there are forty that are utilizable? The question is not 
one of prescribing more or less medicine, but the recognition 
of indications the fulfilment of which is necessary or useful 
when such can be done without harm to the patient. 



8 



CHAPTER VI 

PRIMUM NON NOCERE! 

How can one do harm? How can one avoid doing harm? 

HOW CAN ONE DO HARM? 

Primum non nocere! This precept should be the motto 
of all writings on therapeutics, as it always forces itself upon 
the mind of every conscientious physician at the moment 
when he prescribes. 

It is so easy for a physician to do harm! An inaccurate 
adaptation of means to needs, whether through defect, excess, 
inopportunity , error, ignorance or negligence, may more or less 
disturb the course which the morbid evolution would follow 
under the influence of a strictly adequate adaptation. There- 
fore, having studied the useful actions, it is necessary not to 
overlook, from the view-point of scientific therapeutics, the 
harmful actions. 

Harm is done by defect when the remedy which would cure, 
favor cure, or soothe is not prescribed or is prescribed in insuffi- 
cient doses or is insufficiently prolonged. Thus lesions are 
allowed to become fixed or disturbances to return which might 
disappear if a little more energy or determination had been 
displayed by the physician. Mercury, quinin, digitalis, col- 
chicum, salicylates must be prescribed without delay and 
in fair doses in cases in which they are necessary, and at 
times employed by procedures of the most rapid and active 

114 



PRIMUM NON NOCERE! 115 

action (pernicious paroxysms, gumma of the brain or of the 
palate, threatening asystole). In such cases to wait is to do 
harm. Mercury must be prescribed with interruptions, for 
years. To relax treatment in the presence of deceiving 
assurance of apparent benignity is to run the risk of doing 
harm. In another order of ideas, harm is done when a 
patient is allowed to be asphyxiated by an enormous pleural 
or pericardial effusion, to become emaciated by an inade- 
quate diet, or to be weakened because of defective hygienic 
conditions, or even when a person whose mode of life and 
diet is defective is kept, without warning, on the verge of 
disease. 

The shortcoming of a necessary prescription may be due 
to skepticism, to negligence in securing all the information 
concerning the patient, and to excessive diffidence. The 
physician's art is made up of confidence, prudence, and 
decision — qualities without which the practitioner, with all 
his sciences, would be unequal to his task. 

Harm is done by excess far more frequently than by too 
great moderation: to administer a useless remedy or medi- 
cine in overdoses or for too long a time, to overstimulate an 
organ or to subject a suffering organ to strong medicine, to 
permit accumulation within the same organism of medicines 
which respond to the same symptom or, on the contrary, 
mutually attenuate their effects, to advise exciting measures 
for excitable patients and depressing measures for asthenic 
patients, to overfeed patients who have untrustworthy digest- 
ive organs, to bleed a very depressed patient, to tap a moder- 
ate or scanty pleural effusion, to abuse medicines that are 
new and insufficiently understood are illustrations of harm- 



116 PRINCIPLES OF THERAPEUTICS 

ful actions by excess. We should not, therefore, content 
ourselves with noting the pallor of the face in a nervous woman, 
and prescribe iron without ascertaining whether the paleness 
is due to habitual contraction of the peripheral capillaries. 
We must not mercurialize a syphilitic patient until he pre- 
sents some phenomena of intolerance and loses his teeth 
before we suspend the medication. We must distrust poly- 
pharmacy, avoid direct toni-cardiac, that is, myocardiac 
remedies in large doses in subjects whose myocardiums are 
intoxicated or inflamed. Nor must we send an excitable 
consumptive with congestion and hemoptysis, to a high 
altitude or to the seashore, nor, lastly, believe that every 
anomaly presented by a patient is to be combated by some 
medicinal measure, etc. All these actions are censurable 
excesses. 

Excess in active medicines and therapeutic procedures 
originate either from inadequate knowledge of the pharma- 
codynamic action of remedies and of the activity of natural 
modifiers, or from erroneous deductions as to the needs of 
the patient, or especially from exaggerated confidence in the 
power of therapeutics. A rash or overactive mind is more 
harmful than a diffident one, because if the latter at times 
withholds some useful assistance, it is at least to be suspected 
as an accomplice, while the former may inflict considerable 
harm through its own actions. 

A medicine is harmful through inopportunity when it exerts 
a wrong influence upon the organs of reception, of passage, or 
of elimination. Thus creasote, mercurial preparations, iodin, 
and many others are inopportune for dyspeptics; aloes is bad 
for those suffering from piles; cod-liver oil is not suitable for 



PRIMUM NON NOCERE! 117 

those suffering from diarrhea. Vesicatories may prove very- 
harmful to children, the. aged, and subjects afflicted with epi- 
thelial nephritis. It is likewise inopportune to seek for the 
better when good is at hand. Let me explain: when we 
possess a medicine so specifically precious as is salicylate of 
soda, which cures articular rheumatism in a few days, we 
would be doing harm if we should prescribe only the metallic 
ferments which do not offer the same specificity of action. 
Where traditional medicine has shown the harmlessness and 
regularity of action of certain successful practices, it is inop- 
portune to try to do better by some novel doubtful 
method. 

There is still another kind of inopportunity which consists 
in a disproportion between the treatment prescribed and the 
resources of the patient. It is as unwise to prescribe for poor 
people luxurious medicines, remedies, and regimen or such 
that are too expensive for their situation as it is not to insist 
upon the acceptance of the best measures by the rich for the 
restoration of their health. In fact, it is possible to bestow 
very extensive care upon persons of modest means by concen- 
trating their resourses on the truly useful things. They have 
then to omit from their budgets the excesses of alcohol, wine, 
and tobacco and they must also learn to eat correctly and 
economically. There will then be a fair surplus which can 
be devoted to the re-establishment of health. It is a matter 
of no great difficulty to enable people of modest means to 
enjoy by various combinations the same resources as do the 
richest: solutions instead of potions, packages instead of 
wafers, suitable food-stuffs instead of reparative medica- 
ments, at times a lesson on the practice of hypodermic in- 



118 PRINCIPLES OF THERAPEUTICS 

jections, enemata often substituted for these injections, and 
a hundred other little devices calculated exactly to adapt 
an efficient therapeutics to the patients' means. 

Errare humanum est. He that has never made a mistake, 
let him condemn those who have. The physician who makes 
a mistake after having devoted all his attention, all his con- 
science, intelligence, and knowledge, is not culpable; the 
more so as medicine itself is yet far from perfect, and it may 
mislead the most conscientious by the despairing complexity 
of its subjects of study. The chances of error will diminish 
in proportion as the science advances and the physician is 
better instructed. In spite of all, doing harm by mistake 
may happen and will always happen, at times even in the 
case of the ablest, because this is a human condition. Ad- 
vanced age, the weakening of the senses, personal preoccupa- 
tion, fatigue of body and mind under the influence of pro- 
fessional overwork, too large a number of patients, which 
limits the time devoted to each, sentiments of very strong 
affection, certain defects of character, particularly obstinacy 
and conceitedness, love of paradox and contradiction, impa- 
tience, tendency to simplify things too much, a spirit of sys- 
tem, tendency to imagination, will always be apt to lead 
to mistake. 

All that can be hoped for is to limit as much as possible 
this cause of harmful action, by reinforcing medical studies, 
by establishing the instruction of therapeutics on an ade- 
quately large basis, and by rendering professional education 
as perfect as possible. 

The gravest of harmful actions is insufficiency, which is 
not to be confounded with error. Insufficiency leads to 



PRIMUM NON NOCERE! 119 

gross and habitual errors, different from exceptional error 
resulting at times from the inevitable circumstances above 
alluded to. To appreciate the error of insufficiency is, how- 
ever, a matter of difficulty, unless it be a case of elementary 
mistake, which is not often met with. To incise a vein 
lengthwise for bleeding, to vaccinate by numerous and enor- 
mous incisions (where sight and short scarifications would 
be ample), to give hot baths to depressed patients, to insti- 
tute intensive mercurial treatment for a patient afflicted 
with renal syphilis without regard to the action of this rem- 
edy upon the kidneys, to treat whooping-cough in its be- 
ginning by open windows (a paradoxical practice that has 
cost the lives of numerous children), to immobilize a frac- 
tured limb by placing the fragments in a vicious position, 
to apply an ice-bag on the skin without the interposition of 
a flannel compress, to prescribe emmenagogues to a cachectic 
woman in whom the menses has been arrested, failure to 
recognize the necessity of asepsis in minor, as well as in 
major surgery, to prescribe certain medicines not knowing 
them well or attributing to them an exaggerated potency, 
being misled by some previous fortunate coincidence mis- 
taken for a rule, to irrigate too frequently a cavity which 
is in the process of cicatrization or the seat of a hemorrhage. 
In another order of ideas more difficult to appreciate, to 
impede the urinary depuration of an infected or intoxicated 
subject by remedies apt to obstruct the kidneys (morphin, 
antipyrin, intensive vesicatories), to give a medicine syner- 
getic with the morbid action, to give dangerous medicines in 
toxic doses or too long, are illustrations of unskilful 
management. 



120 PRINCIPLES OF THERAPEUTICS 

There is no doubt that every serious person would regret 
such gross mistakes which are never made by physicians 
who have received a correct medical and therapeutic edu- 
cation. Only lack of education would excuse errors of this 
kind. The physician with an inadequate education, being 
obliged to prescribe, is led to supplement his insufficient com- 
prehension of the case and of its proper treatment by im- 
agination or theories which he improvises; but as knowledge 
cannot be improvised, even with good sense and good will, 
he runs the risk of falling into error. It is true, at the same 
time, that those who remain in their insufficiency, are hindered 
by false pride or lack of energy from devoting themselves 
to additional studies and minute observation. 

There is another way of doing harm; namely, negligence. 
In some cases this is the fault of the person himself, and a 
thorough medical education alone can remedy it; in other 
instances it results from insufficiency of elementary educa- 
tion. The physician who errs in asepsis, or who, intrusted 
with the duty of giving an anesthetic, takes too much interest 
in the operation; he who transports a contagious disease 
from one family to another owing to his neglect to isolate 
himself by a special garment or to wash his hands; he who, 
in a family where a contagious case exists, does not do all 
that is possible to protect the other members from the con- 
tagion; he who permits bed-sores to appear and gives them 
no attention; he who, in cases of typhoid, paraplegia, or any 
of the infectious or nervous diseases, overlooks the proper 
evacuation of the urinary bladder; the forgetful one who 
prescribes a certain dose of which he is not sure or who does 
not stop administration of a medicine in due time; he who 



PRIMUM NON NOCERE! 121 

irrigates the uterus with a liquid too hot or too caustic, etc., 
etc., does harm through negligence. 

There is more. Guilty of negligence also is the physician 
who does not insure the proper execution of his prescriptions, 
or who fails to control the service of the nurses, especially 
if he himself has recommended them, or who does not see 
that the medicines delivered by the pharmacist are of good 
quality and properly prepared: in a word, a physician must 
know that he assumes the moral responsibility not only of 
what he prescribes, but also of the proper execution of his 
prescriptions. I. would like to reverse the Latin axiom and 
say: Be minimis curat medicus. 

Of these various manners of doing harm, some are due, 
as already stated, to insufficient therapeutic education and 
others to insufficient general medical education. 

I cannot too strongly emphasize that I would not dare to 
hold the physician responsible for his shortcomings. There 
are established conditions of duration of study, examina- 
tions, and a diploma, and when a student has satisfied all 
these conditions he is authorized to practise. Is it, then, 
his fault if he has not acquired a knowledge of practical phar- 
macodynamics which nobody has taught him, or he is ignorant 
of pathological physiology which has scarcely been touched 
upon? Under actual conditions medical instruction is in- 
sufficiently organized except for those who are richly gifted. 

It is a grave mistake to think that a young physician can, 
by his own experience, attain an acceptable practice. In 
order to acquire experience it is not enough to see, one must 
know how to observe. Now, in order to observe well one 
must have a very fine education of the senses and know a great 



122 PRINCIPLES OF THERAPEUTICS 

deal. Only those physicians who possess these qualifications 
of instruction and education can profit by observation and 
turn their experience to advantage. 

A word about formularies. To take a book of formulae as 
a basis for prescription would be to make a bad use of it. A 
formulary, no matter how good, can do no more than indicate 
the usual doses, applicable to the generality of cases and to 
habitual indications; but it cannot foresee such and such a 
case under treatment, with its susceptibilities and special 
indications. It is, therefore, not too much to say that one 
may kill by conforming to a very good formulary. 

I take one of the best works of this kind, excellent from 
every standpoint, and open at the word digitalin. I read 
that its dose is from 1/10 mg. to 1 mg. The author has 
evidently in mind stimulation of the heart in the course of 
cardiopathy and has given an exact posology; he could not 
do more. -But if some one, ignorant of the pharmacody- 
namics of digitalin, were to administer 1 mg. of this drug, or 
only half of that dose, in a case of infectious cardiac asthenia, 
in typhoid fever for instance, would he not run a great risk 
of seeing his patient succumb? The danger would be the 
same in all infectious diseases if the heart was much affected 
by intoxication. 

This conclusion may appear somewhat strange in regard to 
pneumonia, as digitalis is an approved medicine for plain 
pneumonia. It has even been said that this medicine acts 
as a functional agent to maintain the integrity of the heart's 
strength. Is this quite certain? If it is true, why is it that 
the other tonic-cardiacs do not exert the same favorable 
action? Digitalis acts in lobar pneumonia in a very partic- 



PRIMUM NON NOCERE! 123 

ular manner. This fact and the interpretation given to it 
as a successful cardiac tonic have led to the administration 
of digitalis in all cases of pneumonia and broncho-pneumonia. 
But the results have not always been favorable and failures 
have been recorded. According to my observation, these 
failures occurred in instances in which the heart expressed its 
affliction in abnormal acceleration and modification of the 
heart sounds, consisting either in suppression of one of them 
or in an embryocardiac tendency. If I am not deceived, 
digitalis is contraindicated in these cases because of the cu- 
mulative action exerted upon the same organ, as I have 
repeatedly stated, of a medicinal poison and a very active 
morbid poison. How could a formulary intended especially 
to furnish practical details on the administration of medicines 
discuss such views? 

HOW CAN ONE AVOID DOING HARM? 

Take, for example, a more commonplace and less delicate 
medicine, sulphate of magnesia. The doses indicated in the 
formulary are from 15 to 60 grm. What would happen if, 
without considering either the intestinal lesions or the stage 
in which perforations and hemorrhages usually occur, and 
taking posology as the sole basis, a physician should prescribe 
only 30 or 40 grm. of the salt in a case of typhoid in its 
third week of development? There may be no evil results, 
but a fatal intestinal perforation may be produced in conse- 
quence of a traumatism inflicted upon an ulcerated intestine 
in its minimum of resistance. Therefore, a dose probably 
harmless (although too large because useless) at the outset 



124 PRINCIPLES OF THERAPEUTICS 

of typhoid fever, may prove fatal in the third week of the 
same disease and for the same patient. 

Therefore, in order not to do harm, it is necessary to take 
into account something more than posology, namely, the 
patient, the disease and its stage of development, and the 
medicinal action, which no formulary can furnish. 

What shall we think of tables of maximum doses? As I 
have myself been guilty of the elaboration of one, I may be 
severe with them. They are worse than useless, for they may 
warrant dangerous therapeutic procedures. 

Almost all posology, based as it is on the theories of phys- 
iological therapeutics, should be revised and reduced. Only 
specific doses and a few others derived from ancient empirical 
practice, as in the case of ergot, established by clinical ob- 
servation, should be maintained. 

The application of primum non nocere would lead us to 
review all the absolute or relative contraindications of medi- 
cines. There are some of a commonplace order, for instance: 
not to prescribe, as a rule, a medicine which may act in the same 
direction as the disease. However, there are exceptions to 
this rule: a purgative may at times be given with benefit 
to a patient suffering from diarrhea, or an emetic to one 
troubled with nausea, because the medicine co-operates with the 
natural process to the same end, viz., evacuation. But no de- 
pressant should be given to a depressed subject, nor an ex- 
citant to a patient or an organ that is excited, nor an irritant 
diuretic to a nephritic subject, etc. 

Furthermore, in order not to do harm, certain conditions 
relative to execution of the prescription must be fulfilled. A 
good prescription should be simple. If it is too complicated, 



PRIMUM NON NOCERE! 125 

it is in danger of being ill carried out or not being followed 
at all. A formula may be above reproach from the stand- 
point of the indications and posology, and yet be apt to do 
harm. For instance, if there is put in the same package of 
powder 1 grm. of one substance, some centigrams of another, 
and a few milligrams of a third, the chances are that, the 
mixing not being thoroughly done, such and such a sub- 
stance, which is prescribed in milligram doses, is not found 
in a certain part and is found in too large amounts in certain 
other parts. Here is, for instance, a formula designed to 
soothe the pains of an aged ataxic man, whose heart often 
presents phenomena of insufficiency. It is irreproachable 
from the view-point of indications and the precaution taken, 
in adding a cardiac tonic in order to avoid the possible de- 
pressive action of phenacetin upon this patient; it has also 
the advantage of being very efficient; nevertheless it is 
defective : 

Phenacetin, . 25 eg. 

Hydrobromate of quinin, 

Pyramidon, aa, 0.15 eg. 

Caffein, . 05 eg. 

Sulphate of spartein, . 005 mg. 

For one wafer. 
F. 30 similar wafers. 

It is obvious that, if the mixture is not quite homogenous, 
one wafer may have too little and another too much of spar- 
tein. To obviate this possibility, it would be prudent to pre- 
scribe, if one must prescribe it, only eight or ten wafers at a 
time. Then each wafer containing only . 605 of the mixture, 
none of the substances could be contained therein in doses 
large enough to prove harmful. 



126 PRINCIPLES OF THERAPEUTICS 

There is a mode of prescribing which is handy and very 
often employed, but which is apt to give rise to trouble. I 
refer to the prescription of the dose of one pill or one pack- 
age. The pharmacist is then obliged to perform an arith- 
metic operation, and he may possibly miscalculate. The 
physician himself ought to assume the task of calculating. 

Let us bear in mind that Article V of an ordinance of 
October 29, 1846, obliges physicians to write in full the dose 
of poisonous substances, and that usage demands indication 
of the number of drops in Roman figures, and that the 
word drop or guttge be written in full. 

We have already spoken of alternation of medicines. An- 
other precaution, which is applicable to the majority of active 
substances, is the division of doses. In proportion as the 
doses are divided, there will be less danger of ever exceeding 
by far the tolerated dose if the patient is carefully watched. 
Division of doses has, however, a limit indicated by the re- 
pugnance of patients to take a medicine too frequently and 
by the necessity of allowing a sufficient interval for ali- 
mentation and other medicines. At any rate, there are cer- 
tain medicines that cannot be divided, such, for instance, as 
the majority of hypnotics, and others which act more ef- 
ficiently in a rather large dose, as quinin in malaria. 

Another device of prescription calculated to obviate dele- 
terious effects consists in the addition of a functional correct- 
ive to an active medicine. Thus in case we have at our dis- 
posal only an antipyretic that is liable to depress the heart, 
we add to it a small quantity of caffein or sulphate of spartein. 
The same precaution may be taken by adding a little sul- 
phate of spartein to hypnotics for those patients whose hearts 



PRIMUM NON NOCERE! 127 

may be depressed by these medicines. For the same reason 
this cardiac stimulant is of great service in chloroform anes- 
thesia. Formerly a little opium was added to mercurial 
preparations in order to prevent colic and diarrhea. 

In conclusion, in order not to do harm, the physician must 
have science, conscience, and art combined. Should there 
be incompleteness, conscience is preferable to science, since 
conscience leads to science, while the converse is not so cer- 
tain. In case of doubt, a conscientious physician will care- 
fully take every measure to avoid a harmful action. It will 
become gradually a habit with him to ask himself certain 
questions whenever he comes face to face with dangerous 
situations. The questions that must always be kept in 
mind are concerning the indications, dosage, contraindica- 
tions, tolerance, and material errors. 

1. What therapeutics, nosocratic, organic or functional, 
symptomatic or reparative, is to be instituted? 

2. If the scheme of therapeutics is nosocratic, what dosage 
is permitted, namely, with what doses is one sure not to ex- 
ceed the limit of tolerance in the particular case? Does this 
patient present any abnormal reactions, any renal, hepatic 
digestive, nervous, or cardiac weakness liable to diminish 
his tolerance? 

3. If the method of treatment is functional, which is more 
delicate, what are the disturbed functions and how are they 
produced? Does their diagnosis offer clearly the characters 
of certainty? Is their prognosis of a nature to warrant inter- 
vention? Are the organs upon which the disturbances depend 
in a state of simple asthenia, or are they affected by an intoxi- 
cation or an active lesion? How is the disturbed function to 



128 PRINCIPLES OF THERAPEUTICS 

be corrected? If this correction can be realized by means of 
a medicine, what is the useful action of this medicine? What 
are the organs and tissues upon which it will exert its selective 
action? What is the dose with which we can be sure to re- 
main on the safe side of the limit of intolerance in a subject 
of medium resistance? Are the organs of the patient under 
consideration able to endure this same dose without intoler- 
ance? Will the medicine under consideration exert its action 
upon the same organs upon which the disease is acting? Is 
there any way of securing the desirable effect by acting in- 
directly through one or several other sound organs? What is 
the posology to be adopted — not to avoid a poisonous action, 
but to adjust it as accurately as possible to the functional 
needs and resistance of the organs to be acted upon? 

4. If the therapeutic arrangement is symptomatic, is it 
necessary to overcome or to suppress the symptom? Is 
there no serious inconvenience in so doing? Can the desirable 
result be obtained without medicine? If a medicine must be 
resorted to, what are the adjuncts whose employment will 
enable us to use as small a dose as possible of the sympto- 
matic remedy? Will the symptom reappear after the me- 
dicinal action is exhausted? In that case, will there be no 
inconvenience in renewing the impression of the medicine? 

5. Is the state of the patient's organs and their functional 
activity noted with sufficient accuracy and completeness to 
enable us to recognize and follow the modifications produced 
by the medicine, in order to continue, reinforce, or suppress 
the medicine according to the effect observed? How will the 
heart, the nervous system, the kidneys, the liver, and the 
digestive organs behave after the patient has received the 



PRIMUM NON NOCERE! 129 

medicines? Is there any fear of intolerance or accumulation 
on account of some insufficiency in the organs of elimination? 
How are the first signs of intolerance to be recognized? 

6. If the question is one of reparative therapeutics, is the 
alimentation sufficient to bring about the desired improve- 
ment? If not, what dose of the medicine under consideration 
is most likely to be completely assimilated; that is, without 
inflicting upon the organs of elimination the task of rejecting 
the unutilized portion? Would this medicine be liable to give 
rise to trouble in the organs of reception? 

7. If one is obliged to prescribe a medicine which presents 
some disadvantage, is there any way to correct or attenuate 
it? In particular, is there any reason for alternating or 
dividing the doses or adding some functional corrective? 

8. Do formulae present any defect in the way of error, 
ambiguity, or difficulty of execution? 

These questions may, at first sight, appear too complicated 
or too numerous; but with a little habit in careful arrange- 
ment of therapeutic schemes they are presented almost 
mechanically to the mind, which solves them readily. Should 
any effort become necessary, it is to be made in order to con- 
form to the first precept of medicine: primum non nocere. 



CHAPTER VII 
THE ELEMENTS OF THERAPEUTIC INDIVIDUALIZATION 

Elements of therapeutic individualization divided into four groups 
relative: 1. To the subject (sex, age, temperament, constitution^ diatheses, 
decay) — 2. To organs and functional activities — 3. To the nature of the 
disease — 4. To the reactions of various organisms to medicinal impres- 
sions (tolerance, inactivity, inertia, intolerance, habituation) . 
» 

The good 'physician is he who succeeds best in individual- 
izing his therapeutic schemes; that is, in prescribing for a given 
patient the corrective which is exactly necessary to him, by adapt- 
ing it as fairly as possible to his proper individuality, in 
order to obtain therefrom the maximum of utility without 
ever doing harm. This individuality results from four groups 
of elements: 1. Elements of the subject in his usual state of 
health. 2. Modifications undergone by the organs and func- 
tions under the influence of the disease, and from which the 
indications are derived. 3. Nature of the disease. 4. Reaction 
of the patient to therapeutic agencies. These diverse ele- 
ments constitute as many sources of variability in the patient's 
physiognomy and reactions. All must be taken into consider- 
ation by the physician when prescribing. Without under- 
taking to enter upon an analysis in all its details (analysis 
which cannot be made with utility except at the bedside), 
we shall study the chief features and endeavor to show their 
importance. 

130 



ELEMENTS OF THERAPEUTIC INDIVIDUALIZATION 131 



I. ELEMENTS WHICH CONSTITUTE THE INDIVIDUALITY 
OF A SUBJECT IN HIS HABITUAL STATE OF HEALTH 

These elements are: sex, age, temperament, constitution, 
diatheses, and cachectic conditions. 

Sex. — In speaking of the reactions occasioned by a medi- 
cine or in formulating dosage, the subject is assumed to be 
of the male sex and of a robust or, at least, average consti- 
tution. Our ideas of reactions, when applied to a woman, 
cease to be exact. The reaction of women to disease and to 
therapeutics offers a very particular physiognomy. 

Women, who furnish surgery its most brilliant successes, 
are also excellent patients for medical therapeutics: by their 
docility and habitual punctuality in following the doctor's 
prescription, by their confidence, by their resignation and 
patience in confronting disease, by their intelligence of the 
details of treatment, they give themselves up, so to say, to 
the discretion of the learned therapeutist and seek no more 
than to turn to profit his ability. But the physician will 
not derive ail possible benefit from these qualities unless 
he is able to penetrate well into feminine individuality, ren- 
dered essentially mobile by the impressionability .of her nerv- 
ous system and by the incessant succession of causes of nerv- 
ous perturbations, such as menstruation, marriage, pregnancy, 
lactation, menopause, domestic worries, not infrequently 
even a usual state of morbidity dependent upon some tena- 
cious disturbance of the utero-ovarian apparatus (metritis, 
salpingo-ovaritis) or chloro-anemia of whatever origin. There 
is another very important point of the feminine individuality 



132 PRINCIPLES OF THERAPEUTICS 

not to be overlooked by the physician, that is the facility 
with which ideas become fixed in her mind. The result is 
that affectional disturbances are, as a rule, more deeply and 
longer felt by her than by men. Hence the necessity, on 
the part of the physician, to weigh well his words, as his words 
produce a telling impression upon her. 

The special sensitiveness of women has led to the rule that 
the dosage of medicines should be for her one-third smaller 
than for an adult man of the same age. This rule is very 
inadequate. During the menstrual period, for instance, 
many medicines are illy borne, even in small doses. It is 
therefore well to discontinue those that are not urgent, some 
of them because of the congestion they produce in the uterus 
(aloes), others because of their direct action upon uterine 
hemorrhage, whether by diminishing, preventing (ergotin, 
opium, ratanhia), or increasing it (salicylate of soda). Quinin 
appears to have a double effect. In principle, its vaso-con- 
stricting action, in small doses, renders it hemostatic (N. 
Gueneau de Mussy, Liegeois, Huchard); it may, however, 
render it emmenagogic, if the case is one of congestive 
dysmenorrhea (Dalche, Soc. de therap., 1900). In large doses, 
quinin is a vaso-dilator and favors particularly venous dila- 
tation; hence, a possible increase in the physiological hemor- 
rhage. In fact, if these foreseen conditions are realized, 
the most opposite effects are observed, which is undoubtedly 
due to variable concomittant action upon blood-pressure 
and upon the energy of the heart. We may be sure only of 
the hemostatic action of small doses, and none should be pre- 
scribed during the menstrual period unless there are urgent 
indications. 



ELEMENTS OF THERAPEUTIC INDIVIDUALIZATION 133 

The menstrual period also is a contraindication for anti- 
thermic medicines, as dangerous depressants; it must dictate 
reservation in regard to excitants which increase nervousness 
(caffein). Feminine sensitiveness during the menstrual period 
(perhaps more exactly during the time that precedes it and 
the first days of its establishment) is such that most women 
fear the use of medicines, even if these should appear to be 
incapable of doing any harm; but the importance of auto- 
suggestion is so great that these repugnances should be re- 
spected whenever there is no necessity to do otherwise. In a 
case of gravity (pernicious paroxysms, appendicitis, hemor- 
rhage, etc.), it is evident that all considerations of a physio- 
logical order would vanish. But do we understand so well 
the action of all medicines upon the organs of generation and 
the modifications which the latter might reflexly exert upon 
the various functions as to expose ourselves, without neces- 
sity, to the production of useless medicinal disturbances? At 
any rate, a great number of drugs (mercury, iodids, iron) 
demand interruption, and the menstrual period offers the 
opportunity of introducing interruptions with advantage. 

During pregnancy therapeutic intervention is still more 
delicate. Quinin, ergot, drastic purgatives, in a certain meas- 
ure salicylate of soda (not to mention the abortives), are capable 
of producing abortion in women predisposed thereto. Great 
prudence is to be exercised if there is albuminuria or renal 
insufficiency or circulatory disorders. Depressing antither- 
mics and hyposthenizants are to be feared. Reflex vomiting 
should not be aroused. Last, but not least, are to be avoided 
the very active drugs which are capable of disturbing the 
vitality of the fetus. 



134 PRINCIPLES OF THERAPEUTICS 

During lactation, except when there is absolute indication, 
we must avoid medicines that are apt to diminish the milk 
secretion (strong purgatives, antipyrin, camphor, apiol, pilo- 
carpin, diuretics, belladonna, iodids, artemisia), and use 
with moderation those which, eliminated through the milk, 
may prove injurious to the nursling (opium, belladonna), 
and even those that may impart a disagreeable taste to the 
milk, such as absinthe, garlic, and probably valerian and asa- 
fetida which communicate their odor to all the secretions. 

Age. — It is a fact open to common observation that chil- 
dren offer a special susceptibility and reaction which necessitate 
a very particular posology. This posology is not exactly 
proportionate, according to age and weight, to that of adults, 
so that there would be no great practical utility to record 
the tables of Juncker, of Gaubius, and others. No one would, 
I believe, found upon them a delicate prescription intended 
for a child. ■ The posology for adults is too far from being 
well-fixed and determined to serve as a safe basis for a deduct- 
ive therapeutic appreciation. Infantile posology, for each 
age, can be determined by clinical experience alone; it cannot 
be derived from any precise law. 

At all events, various authors (Juncker, Gaubius, Cot- 
tereau, Blarez, Baginski) are by no means agreed as to the 
relationship to be established between the posology of the 
adult and that of children; nor is it certain, indeed, that such 
a relationship can be established otherwise than upon approxi- 
mative empirical data. At all events, no terms of a rigor- 
ously accurate relationship are known as yet. Weight, ac- 
cepted by the majority of authors, is altogether defective, as the 
relative weight of the organs taken separately, i.e., apparently 



ELEMENTS OF THERAPEUTIC INDIVIDUALIZATION 135 

the one of the highest importance, varies in enormous pro- 
portions. Thus at birth the weight of the brain is about 
one-eighth of the weight of the body, whereas in the adult 
it is but one-fortieth. Let us note that Fonssagrives is 
tempted to attribute to this circumstance the special sen- 
sitiveness of children to medicines influencing the nervous 
system. 

The fact is that, according to Falck's experiments, the dose 
of strychnin sufficient to cause convulsions is always found 
to be far smaller in very young animals than that necessary 
for adult animals. It is also known that absorption is much 
quicker in children than in adults. 1 The notion of the 
body weight, taken by itself, is therefore an altogether in- 
sufficient basis. 

In practice, however, circumstances may arise in which 
one may regret the lack of an approximative idea of doses 
suitable for children. It is not bad, therefore, to recall one 
of the following empirical procedures that have the merit 
of simplicity 

Young's 'procedure: 

Numerator = age of child 

Fraction of dose = — ; 

Denominator = age + 12 

I prefer Durst's procedure, with an invariable denominator 
of 20, which gives notably smaller doses. 
Durst' s procedure: 

Numerator = age of child. 



Fraction of dose = 



Invariable denominator = 20 



1 It is possible also that their tissues fix more energetically the medicinal 
substances. 



136 PRINCIPLES OF THERAPEUTICS 

Below the age of one year these procedures give too large 
doses. In these cases Durst puts 200 as the denominator and 
fixes the numerator according to the tenths of one year in 
which the child is found. Thus at the age of four or five 
weeks (first tenth) the dose is 1/200 of the dose for the adult, 
and at that of twenty-five weeks 6/200, and toward the age 
of one we find again 10/200; that is, 1/20. 

In reference to the special susceptibilities of children, it is 
necessary to note that their organisms stand very badly 
medicinal antithermics, hyposthenizants, stimulants, antiseptics 
(carbolic acid, bichlorid of mercury, iodoform). 

Among these substances I mark especially the antithermics, 
which should be prescribed with the greatest caution only 
in exceptional cases. If they are administered to feverish 
children, excessive depression of the nervous system and circu- 
lation may result, and several among these drugs are capable 
even of killing. Excepting quinin (which is not always free 
from inconvenience), I would not dare prescribe antithermics 
to- young febrile children, especially if they are feeble and 
nervous. Children may readily develop high temperatures 
which have no grave significance and which, even when they 
assume the character of a dangerous hyperemia by intensity 
or duration, yield too easily to the influence of external cold 
applications to necessitate resort to medicines. Local appli- 
cations to the head, forearms, and hands are often sufficient 
to reduce temperature to an acceptable degree even without 
the intervention of cold baths or moist sheets. In the absence 
of an exact diagnosis and solely for the sake of combating the 
fever, I think there is no occasion for hasty or very energetic 
action. A transient hyperemia is not at all dangerous. I 



ELEMENTS OF THERAPEUTIC INDIVIDUALIZATION 137 

have seen recover a case of pneumonia in the course of which 
the fever rose to 41.7 ° C. in the armpit. It is in such a case 
especially that I would refrain from giving an antithermic 
medicine to a child. 

As to hyposthenizant substances, it is sufficient to bear in 
mind, in order to be convinced of the necessity of great reser- 
vation in prescribing them, that a single drop of laudanum 
administered to a newborn weighing 3 kg. may kill, and 
that even one drop per annum of age, up to four or five 
years of age, if it is not divided, may produce alarming 
somnolence. If this is not a sufficient reason to proscribe 
opium in children, it certainly is a strong reason to render 
us very sparing and to cause us never to give it except in 
fractional doses. 

The harmlessness of chloroform to children is generally 
praised, but it is more exact to say that children are exceed- 
ingly sensitive to this anesthetic and easily sleep under the 
influence of very small doses. Hence the necessity of never 
permitting ourselves to depart in the slightest degree from 
excessive prudence. 

I invoke Dr. Marfan's authority for remarking that mer- 
cury is often prescribed for children in too large doses. Dr. 
Marfan believes that "the nephritis of heredo-syphilitics de- 
velops sometimes under the influence of hydrargyrism." On 
the pretext that children tolerate emetics and calomel well, 
some are tempted to abuse these medicines. I cite again 
Dr. Marfan: "It is necessary to know that an emetic ad- 
ministered to a cachectic nursling may suddenly kill it." 

Bromid and chloral are comparatively well tolerated. 
The same is said to be true of belladonna, although Fons- 



138 PRINCIPLES OF THERAPEUTICS 

sagrives has seen signs of atropinic saturation in children 
under the influence of very small doses. It is advisable to 
guard against the supposed tolerance for belladonna. 

The younger the child the less the need of medicines in 
infantile therapeutics. Before the age of two, employment 
of active medicines is seldom necessary. Polypharmacy is 
more harmful to children than to adults. 1 Hygienic arrange- 
ments, diet, external practices (cold and warm baths, moist 
packs, massage, friction, washing), suffice in most cases. 
Cachectic children are especially sensitive to medicines (Mar- 
fan). General blood-letting should be banished from the 
therapeutics of children under five. Very moderate local 
blood-letting may, in very rare instances, be of service after 
the age of three. 

The aged often present organic affections, particularly 
renal and arteriosclerotic, which necessitate great caution in 
the employment of active medicines. Those that embarrass 
the kidneys (antipyrin, morphin, vesicatories) or depress 
the heart (antithermics in general) should be distrusted. 

Some have advised from the age of sixty on, the adminis- 
tration of doses which would be to those of the adult as a 
fraction whose numerator is 60 and the denominator repre- 
sented by the age of the patient. This is neither a law nor 
an absolute rule, but a practical device which may have its 
utility in determining the reduction of doses for old people 
who are free from taints of all sorts. In many cases (general 
asthenia, arterio- or cardio-renal lesions) even these doses 

1 Chomel reports that Baudelocque who, in his wards of the Hopital des 
Enfants malades, restricted his therapeutics to almost hygienic measures, 
always obtained a smaller death-rate than those of his colleagues who prac- 
tised active therapeutics. ("Pathologie generale," 4th edition, p. 694.) 



ELEMENTS OF THERAPEUTIC INDIVIDUALIZATION 139 

may be too large and may need further reduction. With- 
out departing from prudence, an exception is sometimes 
necessary as regards purgatives, which are often ineffective 
unless given in fairly large doses. 

Temperament, Constitution, Diathesis, Decay. — Thera- 
peutic individualization supposes that each patient is to be 
treated according to his proper reaction, which the physician 
must endeavor to foresee as accurately as possible, in the 
light of the revelations of his clinical examination. The ele- 
ments of this deduction are numerous. They may be grouped 
under four categories corresponding to distinct types. While 
in his reactions each subject always preserves his individu- 
ality, which is probably no more like that of his neighbor than 
are his external aspects, these categories and their subdi- 
visions represent, however, common organic habits which 
draw individuals closer together and enable us fairly to fore- 
see the manner of reaction of each. These categories are 
known under the names temperament, constitution, diathesis; 
we shall add a fourth, under that of decay. There has never 
been agreement as to the meaning of these various designa- 
tions; we shall endeavor to give them greater precision. 

The definition of the word temperament, such as is com- 
monly found in modern classical works, is the one given by 
Dr. Bouchard: temperament is "all that concerns individual 
variations in the intensity of the metamorphoses of the living 
matter.' ' Accordingly, temperament is a dynamic char- 
acteristic, in opposition to constitution which is a static char- 
acteristic looking to the structure of the body. As to dia- 
thesis, Dr. Bouchard defines it as "a permanent disturbance 
in the nutritive mutations which prepare, bring about, and 



140 PRINCIPLES OF THERAPEUTICS 

entertain diseases different as to their symptomatic forms, 
anatomical seats, and pathogenetic processus"; diathesis is 
" a morbid temperament." 

Dr. Bouchard's disciples have adopted these definitions 
which are found almost identical in their works. There is 
a desire to relate all functional or organic activities to the 
intensity of transformation of the living matter, and this 
has become the basis of the theory of "diseases by slackening 
of nutrition." I do not believe these views have been dem- 
onstrated. They remain in the state of interpretation, ap- 
plicable, perhaps, to the generality of facts. On the other 
hand, to characterize temperament by the intensity of nutri- 
tive metamorphoses would be to deny the practical impor- 
tance of the idea of temperament. In fact, what means do 
we possess for appreciating practically, completely, and surely 
the intensity of these metamorphoses? Urology, which 
has been jnade to say too much, can give us but insufficient 
and imperfect notions of their value. The theory of slack- 
ening in nutritive movements has done little for therapeutics. 

For the needs of therapeutics the ancient conceptions, 
more directly demonstrable, would appear much more im- 
portant if they were not also very incomplete. Dr. Bouchard 
declares himself attached to Borden's conception for whom 
"the various temperaments are related to the greater or less 
activity of the organs." But is this identity of definitions 
of Borden and of Bouchard as certain as the latter believes? 
While we clinically appreciate with fair accuracy the degree 
of energy and activity of the organs; while, through thera- 
peutic agents, we know how to modify this energy and this 
activity in a sense generally foreseen, that is, sufficiently 



ELEMENTS OF THERAPEUTIC INDIVIDUALIZATION 141 

known, beyond that horizon we are no longer within the 
domain of certainty. The deeper causes of organic varia- 
tions are still too insufficiently known to be made the basis 
of conception of temperament. In order not to depart from 
the tradition of words, as represented by Borden's defini- 
tion, we should consider temperament as the simple expres- 
sion of an organic and functional predominance. We would 
then comprehend the meaning, though too vague and narrow, 
of the habitual types of the nervous, lymphatic, bilious, and 
sanguine of olden times. 

To-day, however, it is necessary to go a little further. In 
fact, the conception of temperament, as understood by the 
ancients, was very incomplete, since we do not see why there 
should not be as many temperaments as there are organs 
and tissues, and thus add to the number gastric, intestinal, 
renal, etc. 

To this view it may be objected that our actual designa- 
tions of cardiac, hepatic, renal, etc., refer rather to morbid 
types, while the temperaments of the ancients represented 
non-pathological manners of being. This objection would 
be right if, in effect, the word temperament had not at all 
times implied a morbid disposition. The nervous were 
predisposed to affections of the nervous system (hysteria, 
melancholy, mania) and to delirium in acute diseases; the 
bilious to gastro-intestinal inflammations; the sanguine to 
hemorrhages; the lymphatic to chronic catarrhs and cuta- 
neous eruptions, etc. We must recognize that these types 
correspond mostly to cases of neuroses, of cholemia com- 
plicated with intestinal and hepatic infection, and of hyper- 
tension. Consequently, if the temperaments are no longer 



142 PRINCIPLES OF THERAPEUTICS 

much spoken of, it is because their traditional limits have 
been widened rather than that they have been abandoned. 
To the ancient types have been added the renal, the cardiac, 
etc., as representing morbid types just like the old ones. 

But, in the eyes of the therapeutist and the clinician, the 
notion of "the more or less activity of the diverse organs, 11 accord- 
ing to Borden's definition, should prevail, and truly we can 
hardly say much more to-day, or, better, since we have to 
take into account the energy as well as the weakness, the 
integrity as well as the alteration. This definition is not 
open to the reproach of being incomplete, theoretical, im- 
practical, or limited to pathological cases; I believe it will 
endure, having assumed the more precise and correct form, 
given by Dr. Bouchard. There are advantages also in taking 
into account the intensity of the metamorphoses of living 
matter, but this will intervene only accessorily because of its 
uncertainties. For us, therefore, temperament is: all that con- 
cerns the individual variations in the energy and integrity of 
the several organs and in the activity of the nutritive phenomena. 

It has become the custom to designate the exaggerated 
energy of the organs by the prefix hyper and the deficiency 
by that of hypo, and we speak of hyperhepatic and hypohe- 
patic, of hyperthyroideal and hypothyroideal, of a subject 
suffering from hypertension or hypotension, etc. All these 
designations are in the tradition of temperaments. The word 
is seldom employed, but the conception is in the medical 
thought, and is used with greater accuracy than formerly. 

It was, therefore, unjustly that an illustrious English phy- 
sician recently reproached the present generation for not 
sufficiently taking into account the idea of temperament. 






ELEMENTS OF THERAPEUTIC INDIVIDUALIZATION 143 

The knowledge of temperament as defined above is of in- 
contestable utility when a disease begins, since the strong or- 
gans become less weak than the feeble ones; hence the 
necessity of watching the latter with greater solicitude and 
for distrust of such and such a suspicious organ. We must 
not, however, exaggerate the importance of this idea as the 
public is tempted to do. The visiting physician finds himself 
every day in the presence of new patients in the hospital, and 
I am not aware that this circumstance gives rise to real dif- 
ficulties. A thorough analysis of the patient quickly reveals 
the exact value of the organs and their needs, and, withal, 
their respective capacity of resistance. 

Constitution represents more simply the degree of the ap- 
parent vigor of the organism in general; it is robust, weak, 
or average. 

Diathesis seems to me to be essentially different from tem- 
perament. If it were nothing but a morbid temperament, 
as Dr. Bouchard supposes, every exaggeration of a tempera- 
ment would become a diathesis : neuropathy, cholemia, pleth- 
ora would be diatheses. But the latter are precisely states 
which no one has ever thought to call by that name. The 
adherents of the doctrine of irritation had primarily given 
the name diathesis (8ia0eois ; disposition) to the disposition 
of an organ to become affected by some disease. Subse- 
quently the sense of the word was gradually modified so as 
to designate a disposition of the organism to present morbid 
states of the same nature, but differing by their seat and 
appearance. Thus rheumatic, gouty, cancerous, gangrenous, 
dartrous, scorbutic, osseous, aneurysmal, varicose, hemor- 
rhagic, etc., diatheses have been admitted. This conception 



144 PRINCIPLES OF THERAPEUTICS 

should be modernized, and diathesis considered as a mor- 
bid disposition resulting from the impression of specific causes. 
Thus, an ancient syphilitic possesses, even in the absence of 
all syphilitic manifestations, a disposition to develop new 
phenomena: he has the syphilitic diathesis. Similarly, the 
gouty, the rheumatic, etc., present a disposition to new gouty, 
rheumatic, etc., manifestations. 

With all due respect for the high authority of Dr. Bouchard, 
I refuse to regard arthritism as a diathesis, because it has 
nothing specific about it and predisposes to nothing specific. 
I have elsewhere exposed at length 1 the reasons for this 
view, and why I hold arthritism to be a decay of all the tissues, 
rendered more vulnerable and predisposed, on account of this 
inferiority, to the impression of a multitude of different mor- 
bid causes. In fact, arthritics are predisposed to tubercu- 
losis as well as to eczema, to gout as well as to asthma, to 
dyspepsia as well as to nervous exhaustion, etc. Moreover, 
according to my observations, the" general decay is more 
marked in the offspring of the arthritic, and it may be called 
herpetic. 

Beside temperament, constitution, and diathesis, the thera- 
peutist has therefore to take into account decay. Scrofulosis 
(in the absence of tuberculosis developed on it) is neither a 
temperament nor a diathesis. It does not unavoidably pre- 
dispose to anything specific; it represents simply a decline, 
very often originating from syphilis in the progenitors. Like- 
wise, alcoholism is neither a temperament nor a diathesis, 
but a decay. Decay might be classed in the group of consti- 

liC Influence de Parthritisme sur la descendance." Congress for the 
Progress of Sciences. Rheims, August 2, 1907. 



ELEMENTS OF THERAPEUTIC INDIVIDUALIZATION 145 

tution, under the name weak constitution, if there was not a 
difference (of first importance from the therapeutic standpoint) 
between simple feebleness owing to qualitative defect, free 
from any pathological connection, and this weakness which 
results from some taint in the family, or originates from some 
special cause, such as alcohol, syphilis, nervous overstrain, or 
poverty. The state of weakness resulting from a congenital 
inferiority in the quality of the living matter can be modi- 
fied very little, if at all, whereas that resulting from a patho- 
logical condition capable of improvement (syphilis, arthritism, 
or eventual intoxication in the progenitors) can more readily 
be modified. 

Temperament, as we have defined it, is liable to analysis 
and therapeutic indications. The physician will not confine 
himself to-day, like the ancients, to saying that, for instance, 
the sanguine temperament may furnish the indication for 
blood-letting that would be contraindicated in lymphatic and 
nervous subjects; that weakened constitutions cannot well 
tolerate large doses, etc. He will study each organ and each 
function in particular, and will deduce, according to the degree 
of strength, weakness, resistance, failing, integrity, or altera- 
tion of each organ, the arrangement to be made. He will 
thus apply the principles of organic and functional thera- 
peutics as already spoken of at length. In each decision he 
will also take into consideration the elements of constitution, 
decay, and diathesis. 

As an illustration, here is a thin, nervous, pale young woman, 
with a small and palpitating heart, the daughter of a gouty 
or an obese parent. She presents all the attributes that 
Bazin ascribed to herpetism and that are to-day attributed 

10 



146 PRINCIPLES OF THERAPEUTICS 

to arthritism, in spite of the distinction which appears to me 
to exist between these two states. Theoretically, she should 
have a sluggish nutrition, but in reality she presents a com- 
paratively high temperature in the evening; she eats abund- 
antly, as much as her hyperpeptic stomach enables her, and, 
in spite of this circumstance, she remains thin. Suppose 
this subject, as often happens, should some day present with 
exaggeration of the evening temperature a few swollen or 
sensitive cervical ganglia, or even, what is not very rare, 
should, in consequence of exposure to cold, develop an acute 
pleurisy a frigore. And then let us see the case six months 
or a year later. In appearance, she has regained her habitual 
state of health, but she has Koch's bacilli in her system. 
Before the occurrence of any morbid disorder she was simply 
a victim of general decay, but at present she has the tuber- 
cular diathesis, though unattended as yet by any manifes- 
tation of active pulmonary lesion. Should the therapeutist 
now called in to treat her overlook her parents, her decay, 
the state of her heart and stomach, and her local bacillary 
involvement; should he, instead of cautioning her against 
the overactivity to which she is driven by her neurosis, rec- 
ommend exercise, amusement, and traveling, the seashore 
and sunny resorts, the chances are that the tuberculosis will 
involve the lungs, probably in hemoptysic form. If, on the 
contrary, his arrangements should insure for her rest and 
quietude for a few years, a moderate overalimentation adapted 
to a stomach whose glands at first secrete overabundant! y 
and then, at a later period, not enough, also small doses of 
arsenic, strychnin, organic phosphates, perhaps digitalis, 
this patient will gradually grow fat, her decayed system 



ELEMENTS OF THERAPEUTIC INDIVIDUALIZATION 147 

will be built up, all traces of her adenopathies and pleurisy 
will vanish; in brief, she will be restored to perfect health. 

On the other hand, here is a young woman of the same 
age, daughter of a syphilitic. She has all the external symp- 
toms of scrofulosis, with a decidedly slow nutritive move- 
ment and a relatively low temperature She also presents 
ganglionic swellings, more voluminous and more persistent, 
but without fever. Rest, which suited the preceding case, 
will leave this one torpid and ganglionic, and will not safe- 
guard the lungs against involvement. But if this patient 
goes to the seashore, under the direction of a prudent phy- 
sician, if she spends the winters in the French Riviera, where 
the calm and sunny mornings will enable her to spend several 
hours outdoors every day, then her nutrition will become 
more active, the features of her scrofulotic decay will very 
slowly become attenuated, and her recovery will perhaps 
be final. Thus, the tuberculosis germs are observed in two 
different soils, and the subjects get rid of them by two abso- 
lutely opposite modes of treatment. 

Is the question one of syphilis? The mentally active syphi- 
litic subject must be cautioned against general paralysis; 
the lover of sexual pleasures against tabes; the smoker against 
cancer of the tongue. Thus, taking into consideration the 
soil, one may give useful advice for individual prophylaxis. 

Even in cases where the nosocratic character of thera- 
peutics is most pronounced, the individual element inter- 
venes to modify the treatment. The mode of treatment 
will not be the same in the case of a syphilitic or malarial 
subject with powerful digestive organs and in that of a dys- 
peptic. In the former case the stomachal administration 



148 PRINCIPLES OF THERAPEUTICS 

of medicines may be advised, in the latter hypodermic 
injections are to be preferred. The treatment of itch, most 
essentially etiocratic, must vary with the tenderness of the 
skin (particularly in the case of a woman or a child), and 
the degree of the cutaneous inflammation. Thus, under all 
circumstances, therapeutic intervention finds particular in- 
dications in the individual variations of patients. 

Diathesis, as defined above, is often accessible to thera- 
peutics, at least in its manifestations. It requires mostly 
specific remedies (mercury), iodid of potassium, quinin, 
salicylates, etc.), but hygienic therapeutics and mineral waters 
of demonstrated utility are to be resorted to when the diath- 
esis represents the effects of some cause unknown or not 
well known in its essence. Therefore, those predisposed to 
eczema are to be treated by a diet and mode of life especially 
appropriate, and those predisposed to gout, by a special diet 
and certain mineral waters. The weaknesses of constitution 
and decay will find their modifiers, above all, in the repara- 
tive elements of the organism. 

Thus it is seen that diathesis requires both nosocratic and 
reparative therapeutics (medicinal, hygienic, climatic and 
hydromineral) ; temperament, organic and functional thera- 
peutics; decay and constitutional inferiority, reparative thera- 
peutics and hygiene. 

II. THE PATIENT. HIS ORGANS AND FUNCTIONS 

The patient, as already understood in the definition of dis- 
ease (p. 58), presents a set of new reactions which make of 
him, so to speak, a new being. Everything may be modified 
in him: his digestive tract, circulation, elimination, ferment- 



ELEMENTS OF THERAPEUTIC INDIVIDUALIZATION 149 

ation, temperature, defensive reactions, nervous reactions, 
resistance. When the therapeutist comes in touch with this 
new being, whom, after all, he does not know well, since he 
often fails to penetrate at once into the precise meaning of a 
reaction which he calls a symptom, must fear lest he should 
hinder some phenomenon of useful defense or a necessary effort 
for depuration, or add a medicinal to a morbid action, one 
reinforcing the other. This fear, however, must be no more 
than a beginning of wisdom. It would render the physician 
useless if it prevented him from fulfilling necessary indications 
when he possesses the means of effectively so doing either for 
repressing a dangerously intense reaction, or for combating 
or preventing an imminent failure of some organ or function, 
or, lastly, for sustaining the resisting power of the organism. 
It is, I repeat it designedly, by subtle analysis of the patient, 
assisted by very accurate nosographic and pharmacodynamic 
documentation, that the physician will succeed in discovering 
the indications furnished by the state of the organs and in 
choosing the appropriate means to fulfil them. 

The therapeutics of the disordered organs is the one we 
have described under the name organic and functional. There 
is no need of repeating here what we have said of the necessity 
for reinforcing or sometimes moderating the disturbed func- 
tions by means of appropriate " contraries," or of supplement- 
ing the deficient organs by juices obtained from the organs 
of animals, through a new application of "similars." These 
practices are the very essence of scientific therapeutics; they 
constitute the therapeutics of indication, the one which takes 
its point of departure from the needs of the organism. Their 
pitfall is pharmacotoxinic synergy; their advantage is to pro- 



150 PRINCIPLES OF THERAPEUTICS 

cure for the suffering organs the best possible functional activ- 
ity in their anomalous state. Thanks to this intervention, 
the organism will have time to overcome the morbid germs, 
to repair its lesions or to adapt itself thereto; that is, to recover 
if the illness is a curable one; to establish an acceptable modus 
Vivendi if the disease is incurable. 

The new manner of being created by disease is derived, as 
has already been stated, from a series of reactions which bring 
in their train profound modifications in the mode of life to 
be imposed upon the patient. These modifications are of 
two orders : some, hygienic, concern the alimentation, bever- 
ages, environment, and activities of all sorts; to these we 
shall refer in connection with non-medicinal therapeutics. 
The others are related to medicinal influences. Medicines do 
not affect a patient the same way as they do a healthy person. 
These modifications which the elements of disease impress upon 
the organic and functional reactions have been studied very 
little, in spite of their obvious importance. It is by the aid 
of deductions rather than by experimental facts that we have 
called attention to pharmacotoxinic synergies, but a pene- 
trating clinical observation demonstrates their reality. How- 
ever, experimentation does furnish some interesting data rela- 
tive to the influence exercised by a rise in temperature upon 
the action of certain toxic substances. These data are due 
to the labors of Stokvis, Luchsinger, Brunton, P. Langlois, 
Ch. Richet and his disciples. 

Stokvis has demonstrated that frogs are far more sensitive 
to bromid of potassium in water at 32° C. than in water 
at 4° and at 20° C. The experiments of Ch. Richet and 
Railliere demonstrate that hyperthermia increases the toxicity 



ELEMENTS OF THERAPEUTIC INDIVIDUALIZATION 151 

of chloral hydrate. Those of Ch. Richet and P. Langlois 
prove that the convulsivant action of cocain is more marked 
in proportion as the animal under operation is submitted to 
a higher temperature. If the animal is cooled, the convul- 
sions cease. Saint-Hilaire does not hesitate to generalize and 
assert that all rise in organic temperature results in inten- 
sifying toxic reactions/ a conclusion of importance in view of 
the frequency of fever. 

It is a matter of great difficulty to foresee what would be 
the reaction of patients in a state of hypothermia, the more 
so as this state is associated with other generally grave dis- 
orders, as in cholera, grave icterus, uremia, etc. It seems 
probable that every hyposthenizant medicine must be harm- 
ful. A considerable number of observations demonstrate 
that raw alcohol is a harmful medicine to give to a subject 
benumbed by cold; death may result therefrom. 2 

Thus we see that we are far from well acquainted with the 
modifications which the state of disease impresses upon the 
pharmacodynamic action of remedies. Let us also note that 
in spite of the great progress realized, we are just as little 
acquainted with all the elements that intervene to produce 
a particular mode of development of a disease. Clinical 
experience simply teaches that all is not in the apparent 
functions of the accessible organs (heart, kidneys, stomach, 
intestines, etc.), and that, even when we add to these the 
known facts of intoxications and phagocytosis, there remain 

1 Ch. Richet, Soc. biol, April 18, 1885; P. Langlois and Ch. Richet, Acad, 
des sciences, June 4, 1888; Railliere, Th. Paris, 1888; Saint-Hilaire, Th. Paris, 

1888. 

2 A. Manquat, "Traitment des accidents causes par le froid," "Traite* 
de Therapeutique appliquee " of A. Robin. 



152 PRINCIPLES OF THERAPEUTICS 

unknown things. We must also think of the processes of 
fermentation that go on in the depths of certain organs (such 
as the liver) and tissues, of the action of glands with internal 
secretions (thyroid, hypophysis, suprarenal capsules, etc.), 
of the functions of the spleen, of the lymphatic glands, and 
the bone-marrow, of the formation of new substances, some 
of them sensibilizing, others protecting, and of the utilization 
of certain lipoids (cholesterin), etc. 

It is probable that the incessant researches being pursued 
in this direction will penetrate into the exact mechanism 
of morbid actions, the causes which intensify them and those 
which are capable of lessening them. Therapeutics will 
then no longer be considered, as unfortunately it is at present, 
as an aid in the service of some organs (organic and func- 
tional therapeutics) ; but the organism will be given the means 
which it lacks for combating the pathogenic agent or its 
products. Then nosocratic therapeutics will dominate all 
others; it will be less helpless against diseases which develop 
in the aged, the depressed, in subjects prepared by some 
previous infection, in the declining and in the defectives of 
all kinds. 

In fact, patients at times succumb with lesions that are 
not enough of themselves to cause death, and with organs 
still vigorous. If the maintenance of the dynamism of the 
organs in a satisfactory state should suffice, therapeutics 
would less frequently be powerless, for the organs resist dis- 
ease fairly well if they have not suffered too much from some 
former pathological state. A young and sound individual, 
not depressed, attacked by an acute curable disease, such 
as pneumonia or typhoid fever, will not succumb if, from 



ELEMENTS OF THERAPEUTIC INDIVIDUALIZATION 153 

the onset of the malady, he is placed in favorable conditions 
of resistance and defense, and if he does not become a victim 
to improper therapeutic efforts. In other words, this indi- 
vidual has the greatest chances of spontaneous recovery. 
He bears within himself the elements of defense against 
morbid germs and their elements of attack. The reason 
that disease is far more serious in the aged, the depressed, 
and in subjects prepared by some other infection is prob- 
ably because these elements of defense have become insuf- 
ficient. It is these elements that are imperfectly known 
and toward the discovery of which the efforts of investiga- 
tion must be directed. It is through them that we will 
be able to assail disease itself. 

For the time being our main resource lies in functional 
therapeutics, which we must endeavor to render as perfect 
as possible. This therapeutics, besides precision in indi- 
cations, in posology, and in mode of administration, some- 
times requires preparation of the patient to its action. This 
procedure is well known in regard to the employment of 
digitalis in asystole. This remedy is more effective when 
the patient is previously subjected to rest and a plain diet, 
relieved of congestion by means of dry cups applied in great 
numbers to the chest and the region of the kidneys, purged, 
if necessary, and tapped sometimes in case of profuse hydro- 
thorax. Of course, if the case is urgent, the physician should 
not wait for the effects of this preparation, but concurrently 
prescribe digitalis; he should comprehend, however, that 
the less digitalis has to do, the greater its efficacy, since, its 
action being above all exerted through the heart, all that 
otherwise can be done to restore the circulation its equi- 



154 PRINCIPLES OF THERAPEUTICS 

librium will lessen the effort demanded of this organ. De- 
chlorination in Bright's disease is at once a therapeutic pro- 
cedure and a preparation for the action of diuretics. 

There is a method of mixed anesthesia that consists in 
preparing the patient by morphin before subjecting him 
to chloroform; another in washing out the stomach, so as to 
obviate vomiting provoked by chloroform. Another pre- 
paratory procedure is to stimulate the heart by means of 
spartein in order to prevent syncope. Atropin has been 
advised for the purpose of lessening the excitability of the 
pneumogastric. Feeding the patient before subjecting him 
to the action of cocain, and placing him at rest in a room 
protected from light and noise in order to favor the action 
of hypnotics, are other illustrations of preparation for the 
influence of a medicine. As a rule, hygienic always assists 
medicinal therapeutics. 

These Various practices lead to a principle, i.e., whenever 
it is possible, through some non-medicinal means or through 
some relatively harmless medicine, to reinforce the action 
of an active medicine, it is well to do so in order to obviate 
the necessity of intensive action by the latter. 

III. DISEASE 

The kind of disease implies extreme variation in the ac- 
tivity of the same therapeutic agents directed against similar 
morbid states. Curative power and utter inactivity are within 
the limits of these variations, as is seen in the case of quinin 
and salicylate of soda against fever. Physiological physi- 
cians have saught the reason of these differences in pharma- 



ELMEENTS OF THERAPEUTIC INDIVIDUALIZATION 155 

codynamic action. I have shown elsewhere 1 that these dif- 
ferences in effect, when so wide, are due to difference in the 
action of the medicine, which cures as a specific in the success- 
ful cases, and is more or less inert when it cannot directly or 
indirectly reach the cause of the disease itself. 

How is it possible to explain the fact that the fever of ery- 
sipelas resists antipyrin doses which are sufficient to reduce 
the temperature of a typhoid patient to normal and to cure 
a rheumatic sufferer? That a dose of quinin, hardly suffi- 
cient to lower by one or two tenths of a degree the tempera- 
ture in typhoid, can more or less successfully prevent (even 
if not in a final manner) the return of a paroxysm of an hyper- 
pyretic intermittent fever? Dr. Lepine has even spoken of 
semi-specificity and said in reference to quinin in influenza^ 
that it appeared to him to be a semi-specific. I also believe 
that certain medicines whose action is constantly successful, 
like that of quinin at the onset of influenza, exert some degree 
of specific action. 

Thus the species of disease intervenes to fix, in a large meas- 
ure, the mode of therapeutic intervention in the face of a 
determined illness, but without prejudice to relative indi- 
vidualization, as we have already seen and shall further show 
in the following lines. 

IV. DIFFERENT MODES OF REACTION OF PATIENTS IN 
REGARD TO MEDICINES. 

The reactions of patients to medicine are related to the 
state of organs, to special disposition of subjects to respond 
in such or such a manner to the substance given, and to the 

X A. Manquat, "Traite de Therapeutique," 5th edition, Vol. II, pp. 559, 
562 and 563. 



156 PRINCIPLES OF THERAPEUTICS 

repetition of the impression of this substance. Tolerance, 
intolerance, activity, inertia, hyperesthesia and habituation 
result from these various conditions. 

Influence of the State and Disposition of the Organs 
and Tissues upon Medicinal Activity. — It is known that 
medicines intended for absorption are generally more active 
when taken on an empty stomach, because they remain in 
a state of greater concentration and are less liable to undergo 
alteration in their chemical composition, they are, moreover, 
more rapidly absorbed. Such are digitalin, the majority of 
glucosids and some alkaloids. On the other hand, the irri- 
tant action of certain remedies upon an empty stomach is at 
times so injurious that it has become necessary to administer 
them when the stomach is full, in order to dilute them and 
thus spare the gastric mucous membrane. For this reason 
quinin, salicylate of soda, mercurial preparations, iodids and 
chloral hydrate are administered with or soon after meals. 
This procedure is necessary when we desire to modify the ab- 
normal reaction of the contents of the stomach (hyperacidity), 
or to evacuate the gastric contents (emetics, purgatives, in a 
case of poisoning), or to promote their physiological evacuation 
(bicarbonate of soda) . In other instances the digestive period 
is selected because the digestive juices favor solution of the 
medicine; quinin and sulphonal are among the number. This 
same reason necessitates at times careful avoidance of 
the period of gastric activity in order to obviate the formation 
of certain too powerful combinations : white oxid of antimony 
and kermes, for instance, which form tartar emetic in the 
presence of the hydrochloric acid of the gastric juice, would 
produce much more of it during gastric digestion than in the 



ELEMENTS OF THERAPEUTIC INDIVIDUALIZATION 157 

empty state of this organ, so that they would cause nausea 
and even vomiting if ingested during or soon after a meal. 

It is hardly necessary to say that it is not proper to adminis- 
ter, during the digestive period, medicines intended to act on 
the gastric mucous membrane itself (ipecacuanha) or the in- 
testine (saline purgatives, drastics), unless evacuation of the 
contents of the stomach is desired. A few laxatives alone 
can be taken after meals; but it will not be long before they 
also begin to cause irritation by their prolonged action. Re- 
storative medicines (phosphates, cod-liver oil), true aliments, 
are, as a rule, administered at meal time. 

The rules may be briefly laid down as follows: 1. On an 
empty stomach, or between meals, the medicines that are very 
alterable (the majority of glucosids, antimonials), those from 
which the maximum of activity and rapidity of action is de- 
manded (glucosids, alkaloids), those that must act immedi- 
ately and energetically on the digestive tract (emetics and 
purgatives), lastly those that would act unfavorably upon 
the stomach by too prolonged sojourn in this cavity (irritant 
laxatives and purgatives). 2. During the state of fullness of 
the stomach, medicines that are irritants to the gastric mucous 
membrane (salicylate of soda, iodids, etc.), those that are 
intended to provoke evacuation of some deleterious or toxic 
substance ingested with the food (emetics and purgatives) 
or, on the contrary, to favor digestion (pepsin), those that 
require gastric juiee in order to be sufficiently dissolved 
(quinin), those which we desire to have slowly absorbed, 
and, lastly, reparative medicines. 

For a few medicines it is a matter of indifference whether 
they are taken on an empty or full stomach (codein, bromids), 



158 PRINCIPLES OF THERAPEUTICS 

while in the case of hemorrhage or pernicious paroxysm there 
can be no choice of time. At all events, if the stomach is 
empty, irritant medicines must be diluted with a sufficient 
quantity of water. Vigorous scrubbing of the skin with soap 
and brush and washing with alcohol favors cutaneous absorp- 
tion: friction with collargol may be followed by absorption 
only under these conditions. The area of skin to which mer- 
cury or salicylate of methyl is to be applied or rubbed should 
at least be washed with soap and water. 

The subcutaneous cellular tissue, at present so successfully 
employed as a route of introduction of medicines, is intolerant 
for a number of substances which cause pain, inflammation, 
suppuration, swelling. In this respect there are notable indi- 
vidual variations. The same substance injected into one 
patient is painless, while to another it is very painful. Every- 
one should strive to render the injections tolerable, either by 
diluting ttte injected substance (hydrochlorate of quinin), 
or by modifying the chemical composition of the remedy 
(forminate of quinin, benzoate and organic compounds of 
mercury), or by carefully looking for conditions which lessen 
the patient's susceptibility. 

The muscular tissue is more tolerant than the subcutaneous 
cellular tissue, but it is more deeply seated and it is not always 
easy to appreciate its thickness. Therefore, intramuscular 
injection requires accurate knowledge of the distribution of 
nerves and ve se s of the region. 

Circulatory activity is a condition of rapid absorption. 
Edematous cellular tissue will therefore absorb medicines less 
rapidly than the same tissue under normal conditions; those 
injected in the last phases of life have little chance of utiliza- 



ELEMENTS OF THERAPEUTIC INDIVIDUALIZATION 159 

tion. An intervention attempted in extremis would certainly 
have no effect unless practised intravenously (provided there 
be no contraindication on the score of the nature of the liqu d). 

The state of emptyness of the vessels favors the absorp- 
tion and activity of medicines; conversely, their fullness 
diminishes absorption (Magendie 1 ). 

The rectum is a very delicate cavity which must be spared 
in order not to give rise to extremely painful rectitis. There 
are certain medicines that are to be proscribed from rectal 
administration by enema (notably bichlorid of mercury, 
unless the solution is extraordinarily diluted). The adminis- 
tration of less irritating substances and of those that are 
to be often repeated (aliments) should always be watched. 
Enemata intended to be kept are ill endured by hemorrhoidal 
and prostatic subjects. Suppositories are generally better 
borne than enemata. 

Reaction of the Organism to Therapeutic Doses of 
Medicines. — The elements of therapeutic individualization 
hitherto pointed out present difficulties, but the difficulties 
become greater when the reaction of the organism to the 
action of medicines is added to the study of the needs of 

1 Experiments by Stelberger and Erichson on a child afflicted with exstrophy 
of the bladder, whose urine could be gathered drop by drop, demonstrate 
that ferrocyanid of potassium, ingested eleven hours after a meal, appears 
in the urine one minute after ingestion. If it is ingested four hours after a 
meal, two minutes are necessary; if after an hour and a half, six or seven 
minutes; if the interval is reduced to twenty-five minutes, elimination does 
not begin until sixteen minutes after; lastly, if ferrocyanid is taken with the 
meal, it is detected in the urine only after thirty or forty minutes (experments 
reported by Beclard in the "Diet, encycl. des Sc. med.," art. "Absorption"). 
These variations are attributed to the state of fullness of the vessels. More 
recently Adducco (Ac. med. di Roma, 19, fas. 2), has studied the influence of 
fasting: cocain, strychnin and phenol act with far greater intensity on 
animals fasting for several days than on those well fed. 



160 PRINCIPLES OF THERAPEUTICS 

the organism and the means to meet them, i.e., tolerance, 
intolerance, and habituation that constitute the limits within 
which therapeutic action fluctuates. 

Tolerance and Inertia. — Under the name tolerance is 
designated the aptitude of certain organisms to bear, with- 
out inconvenience, large doses of medicines. Tolerance must 
be distinguished from inertia or insensibility, or "apathy" 
(Fonssagrives) to medicines, and from medicinal inactivity. 
Tolerance does not prevent the medicine from acting; it is 
even advantageous inasmuch as it permits increase of the 
dose to the necessary quantity. Thus, a tolerant patient 
will endure a large dose of a hypnotic and sleep, or he will 
stand notable quantities of mercury and recover. Conversely, 
if there is inertia or inactivity, the remedy will fail to produce 
the expected effects. The inert patient will easily bear doses 
as large as those borne by the tolerant, but without deriving 
therefrom .the same benefit. Thus, to take the preceding 
illustrations, he will not sleep under the influence of the chosen 
hypnotic, nor will he be cured under that of mercury, even 
if the doses are large. 

Tolerance is sometimes due to natural disposition, and 
sometimes to disposition acquired through the state of dis- 
ease. The causes of inertia or apathy toward medicines are 
not always appreciable, It may be assumed that, in some 
instances, under the influence of some depressing morbid 
cause, the living matter undergoes such a modification that 
the habitual medicinal action can no longer be exerted. The 
subcutaneous injection of ether, in the agonic phase, is no 
longer perceived and does not produce its usual effects. When 
emetics were used and abused in affections of the respira- 



ELEMENTS OF THERAPEUTIC INDIVIDUALIZATION 161 

tory organs in children (capillary bronchitis, pneumonia, 
diphtheria), it was observed that the emetic effect was no 
longer obtained at an advanced stage. In both these in- 
stances the patient's impressionability is so blunted that he 
cannot respond to the action of the medicine. It is not im- 
possible, as is suggested by Fonssagrives, that insensibility 
to medicines may result also, though very seldom, from in- 
dividual idiosyncratic disposition. 

Shall we ascribe to tolerance or to inertia the disposition 
of pneumonia patients to endure, without emetic and pur- 
gative effects, enormous doses of tartar emetic (0.50 to 1 grm.)? 
This question would carry us to antiquated discussions raised 
by Rasori's school. This resistance to tartar emetic is un- 
doubtedly due to varied reasons; in the first place, to habitua- 
tion. The latter is possible for tartar emetic, since it enables 
the tuberculous to endure large doses of this medicine for 
from ten to fifteen days and longer (Fonssagrives, Bucquoy). 
The same reason may have intervened in pneumonia, since 
tolerance required division of the doses and did not at once 
manifest itself, except in rare instances and in cases of unusual 
gravity. Moreover, tartar emetic blunts the excitability of 
the cerebro-spinal centers and weakens the reflex necessary 
to vomiting. However, it is not un ikely that pneumonia 
patients enjoy a true tolerance in regard to tartar emetic, 
since the majority of healthy persons cannot tolerate without 
serious suffering doses of the medicine far smaller (10 eg.) 
than those formerly prescribed to pneumonia subjects. As 
to doses of 0.50 to 1 gr., they would certainly cause prostra- 
tion, if not collapse. 

These accidents may at times have occurred in pneumonia 
ii 



162 PRINCIPLES OF THERAPEUTICS 

cases treated by tartar emetic; but they cannot have been 
frequent, since such eminent observers as Laennec, Grisolle, 
Louis, Trousseau, and many other physicians of the same epoch 
would not systematically have given a medicine so manifestly 
depressing. 

Tolerance may sometimes be increased under the influence 
of certain pathological conditions. It will suffice to bear in 
mind the well-known special tolerance of pneumonia patients 
to doses of digitalis which would probably never be admitted 
by individuals in a state of health; also the tolerance for alco- 
hol by these same patients who can endure without intoxica- 
tion enormous doses thereof; and the tolerance of tetanic 
patients for opiates and chloral. 

Morphinomaniacs often manifest for years a tolerance as 
remarkable for most medicines as for morphin. The same 
is true of chloral, ether, cocain, alcohol, quinin, heroin, etc., 
but, at an advanced stage, even in the absence of well-marked 
cachexia, these patients often become quite intolerant, notably 
for hypnotics. I have seen a dose of 0.75 eg. of veronal 
cause a morphinomaniac to sleep for sixty hours and then 
leave him in a state of excessive depression. 

Diabetic subjects, owing undoubtedly to their polyuria, 
endure in general the majority of medicines fairly well so 
long as they have not albuminuria; but so soon as the latter 
complication appears, their resistance declines; especially 
antipyrin and morphin, so well tolerated before, no longer 
have the same degree of innocuity. In the absence of albumin- 
uria their tolerance for opium is well known; however, abuse 
of this medicine has been regarded as (Hilton Fagge) favor- 
ing coma. This accident is by no means rare in consequence 



ELEMENTS OF THERAPEUTIC INDIVIDUALIZATION 16,3 

of prolonged or repeated administration of chloroform. At 
all events, accidents (ever fortunate ones) are always to be 
expected in diabetic subjects. 

Let us also mention the tolerance of alcoholic subjects 
for digitalis and opium. Even though alcoholic subjects 
suffering from delirium tremens sometimes tolerate enormous 
doses of opium, the latter not infrequently produces a coma- 
tose state from which the patient fails to recover. These 
examples show that while certain general pathological con- 
ditions seem to favor tolerance in a great number of cases, it 
is prudent not to rely too much upon them and to fear unex- 
pected occurrences that are always possible. 

Tolerance may be obtained or increased by means of cer- 
tain remedies. Thus, syphilitics, submitted to the action 
of sulphurous waters, become tolerant of doses of mercury 
more considerable than average normal doses, because these 
waters facilitate elimination of mercury. Cure by reduction 
of chlorids favors tolerance for alkaline bromids (Toulouse). 
Bicarbonate of soda, belladonna, and milk diet are supposed 
to prevent iodism. Asepsis of the skin obviates iodic erup- 
tions (Fere). Cleanliness of the mouth is certainly indispen- 
sable for tolerance to mercury. I have insisted upon the 
necessity of adding to antipyretic medicines (so seldom 
useful) small doses 1 of heart stimulants in the treatment of 
depressed subjects. 

Inactivity of medicines supposes that the medicine has 

encountered some obstacle which impedes its absorption or 

diffusion, and prevents it from reaching its destination. For 

example, lack of solubility in the digestive tract (sulphonal, 

*For instance £ or 1 eg. of spartein, or 5 to 10 eg. of caffein. 



164 PRINCIPLES OF THERAPEUTICS 

hardened pills), lack of absorption as a result of fever (Briquet) 
or some circulatory disorder, retention at a point of the organ- 
ism (the stomach for instance) which does not absorb well 
or which (the liver) stores up a certain substance. 

In accounting for the reasons for failure of a medicine to 
produce the expected effect, it is often difficult to determine 
whether failure is due to medicinal inertia, inactivity, or 
idiosyncratic resistance. 

Intolerance. — Intolerance is the reverse of tolerance; it con- 
sists in the manifestation of toxic or simply unpleasant phe- 
nomena from doses that usually are well borne by subjects 
of apparently the same constitution. 

It is necessary to distinguish the intolerance which mani- 
festly is due to a pathological or abnormal state of the organs 
or functions from that which seems to result from a special 
reaction, peculiar to the subject. The former may be sus- 
pected; the latter, of much rarer occurrence, will necessarily 
be a surprise. 

The pathological states capable of giving rise to intolerance 
are related to the organs of reception of the remedy; to the 
organs upon which the action of the latter is exerted; and to 
organs apparently independent of the medicinal impression, 
but, nevertheless, in nervous connection with the organs 
affected; also to organs concerned in elimination. Intolerance 
may depend also upon general pathological states, such as 
fever, diabetes, morphinism, etc., as well as upon local patho- 
logical states. 

The organs of reception most readily rendered intolerant 
by a pre-existing pathological state are those of digestion. 
Gastric intolerance is manifested in dyspeptics in connection 



ELEMENTS OF THERAPEUTIC INDIVIDUALIZATION 165 

with a great number of irritant medicines (copaiba, cubebs, 
quinin in large doses, repeated drastics, iodids, etc.); it is 
expressed by a gastric irritation which usually gives rise to 
symptoms of painful hypersthenia or even true medicinal 
gastritis. The altered intestine is similarly irritated by mer- 
cury, repeated drastics, large doses of cod-liver oil, etc. The 
result is diarrhea and, at times, acute enteritis. 

Intolerance of the organs in regard to a medicine which 
exerts its selective action upon them is generally due to the 
fact that such medicinal impression on these organs intensifies 
their natural or pathological tendency. Thus, aloes, which 
produces congestion in the rectum, is illy tolerated by subjects 
suffering from hemorrhoids and prostatitis; under the influence 
of quinin, tinnitus aurium and deafness very readily develop 
in those who already are subject to them; medicinal delirium, 
vertigo, trembling, and palpitation are observed chiefly in 
nervous persons; cardiac collapse attacks especially those 
subjects whose hearts are weakened or depressed, etc. Car- 
diac asthenia necessitates the greatest reservation in the 
employment of medicines liable to weaken the heart (most 
of the hypnotics, particularly chloral in usual doses, antipyrin 
and most of the antipyreties, above all in the feverish). Simple 
nervous depression, which is accompanied by a certain degree 
of cardiac asthenia, necessitates the same caution. When 
cardiac asthenia results from intoxication, it dictates caution 
not only in the employment of hyposthenizants to the heart, 
but also in that of cardiac tonics which exert an energetic 
action upon the myocardium, for fear of pharmacotoxinic 
overcharge. As it is in the case of the nervous that accidents 



166 PRINCIPLES OF THERAPEUTICS 

of intolerance have most frequently been observed, particular 
prudence should be exercised in handling them. 

The value of the organs of elimination plays a most im- 
portant role in the production of intolerance. Urinary elimi- 
nation being the most important of all, no energetic medicine, 
especially if its action is to be prolonged, should be prescribed 
without previous examination of the urine, and at times of 
the permeability of the kidneys. As a rule, any person suf- 
fering from a renal lesion must be considered suspicious in 
the matter of tolerance. Medicines that are apt to disturb 
the function or integrity of the kidneys are especially to be 
distrusted: antipyrin, morphin, mercury, cantharides, uro- 
tropin, alcohol cannot be given for any length of time or in 
large doses to patients suffering from a renal lesion except 
after examination of the permeability of the kidneys, and 
even then they must be given with great circumspection. 

From this view-point, appreciation of renal permeability 
is of greater import than the mere fact of a lesion, since, as 
has been noted by Lecorche, it is only in the ultimate phases 
of nephritis, in the exhausted and cachectic, that intoler- 
ance of medicines is to be feared; during the intermediary 
periods there is much less danger, though it is always possible. 

When the kidneys are insufficient, habitually harmless 
doses of medicines may produce grave disorders. Jaborandi 
and its alkaloid, pilocarpin, may cause nausea, vomiting, 
hiccough, tendency to syncope and to collapse. In a case, 
reported by Oertel, pulmonary edema occurred, and in one 
of Dujardin-Beaumetz's, death. Dickinson, Roberts, Bou- 
chard, and all the syphilographers have noted frequency of 
intolerance for mercury in patients with renal lesions, even 



ELEMENTS OF THERAPEUTIC INDIVIDUALIZATION 167 

though syphilitic. Lecorche accuses chloral (2 to 4 grm). 
of having caused, under the same circumstances, pulmonary 
congestion with bloody expectoration. Chauvet (1877) dem- 
onstrated the slowness of elimination of quinin in nephritic 
subjects. This elimination may persist for a period of from 
four to seven days. Morphin has been a subject of contra- 
dictory assertions. Lecorche, Huchard, and many others do 
not hesitate to prescribe it in cardio-uremic dyspnoea. I 
have seen it so very harmful in several cases of uremic dysp- 
noea that I will refrain from prescribing it in such instances. 
Subjects with mouths in a bad state readily develop intoler- 
ance for mercury, and those whose buccal reaction is habit- 
ually acid show intolerance for iodids. 

It is by no means necessary that a medicine should come 
in contact with, or exert its action upon an organ in order 
to produce phenomena of intolerance; the nervous tract may 
serve as an intermediary. Thus, a subcutaneous injection 
of morphin often causes vomiting. Excessive susceptibility 
of the nervous system favors medicinal eruptions. Above 
all, gastric reflex must be taken into consideration in the 
production of events of intolerance. As soon as the effect 
of a medicine is exerted upon an irritable stomach, the most 
varied reflexes may be induced. If, to make matters worse, 
this effect is feared by the patient, autosuggestion intervenes 
to increase the effects. Under such circumstances the most 
insignificant dose of any medicine may cause palpitation, 
intermittence, vertigo, cold perspiration, and syncope. It 
is a familiar fact that subjects whose stomachs contain food 
and liquid are intolerant for chloroform; conversely, when 
the stomach is empty, cocain is not tolerated. 



168 PRINCIPLES OF THERAPEUTICS 

General pathological states profoundly modify dispositions 
in regard to tolerance. Antipyrin, which is so fearfully abused 
by the public, may give rise in the feverish, especially if the 
temperature is very high, to grave phenomena through the 
combined influence of the abrupt suppression of the cardiac 
stimulation created by hyperthermia and the concomitant 
nervous depression. As has already been noted, elevation 
of the body temperature augments the activity of toxic 
substances. Morphinism, diabetes, alcoholism, in their ad- 
vanced stages, create a state of susceptibility which has been 
referred to in connection with tolerance; all states of cachexia, 
depression, and asthenia favor intolerance. 

The disturbances which sometimes occur in aged gouty 
subjects in consequence of an active medication directed 
against gout, are generally ascribed to arterio-cardio-renal 
lesions. Is this explanation always sufficient? Without 
denying the, participation of such lesions in the production 
of such disturbances, it is also very likely that an intensive 
anti-gouty medication may suddenly mobilize either more or 
less important quantities of uric acid or other substances 
unknown to us retained in the tissues, and thus give rise to 
unforeseen accidents. As long as the pathogeny of gout and 
the mode of action of anti-gouty treatments are not clearly 
elucidated, therapeutic intervention in aged gouty subjects 
must be very moderate and slow. More importance must 
be given to the anti-uricemic diet (well established to-day), 
indefinitely necessary, to mineral waters and hygienic ar- 
rangements, than to medicines often so illy tolerated. 

Morphin, which the physician is sometimes tempted to 
prescribe to relieve the pains of the gouty, is contraindicated 



ELEMENTS OF THERAPEUTIC INDIVIDUALIZATION 169 

in these patients. It may hinder their urinary elimination 
which it is so necessary to maintain intact. For the same 
reason the cantharides vesicatory is to be feared. 

It is sometimes impossible to determine the reason of in- 
tolerance; it is then attributed to a particular state called idio- 
syncrasy. It is an exaggerated reaction of an individual to 
the effect of a remedy. It results from individual conditions 
whose analysis is impossible for the time being. The familiar 
examples relative to alcohol, tobacco, coffee, strawberries, 1 
eggs, etc., demonstrate that the reaction of the living matter 
is far from being the same in different individuals, under 
the effect of usual substances. The same is true of medicines. 
Writers on therapeutics cite numerous cases of idiosyncratic 
intolerance for opium, belladonna, hyoscyamus, tartar emetic, 
antipyrin, quinin, arsenic, and even rhubarb. I have ob- 
served a man who could not ingest a small dose of quinin, 
even 10 eg., without developing soon thereafter a pruriginous 
eruption in two fingers. In certain highly susceptible per- 
sons even a mild purgative may cause alarming syncope. 

Idiosyncrasies, however, seldom produce manifestations 
of intolerance as grave as those resulting from organic lesions 
or general pathological states. With sound organs, the sub- 
ject intoxicated by a dose which, by the very definition of 
intolerance, is always to be moderate, will readily free himself 
of the illy tolerated medicine, while the phenomena of intoler- 
ance dependent upon a renal lesion, cardiac asthenia, or a 
pronounced nervous depression may assume a character of 
the highest gravity and even cause death. Intolerance being 

1 1 knew a young woman in whom ingestion of a single strawberry- 
sufficed to produce itching of the tongue, palate, and throat, then very 
severe pain in the stomach. 



170 PRINCIPLES OF THERAPEUTICS 

a toxic manifestation, nearly all tissues, organs, and functions 
may become the seat of a reaction of this order, under the 
influence of an active medicine. 

The skin is apt to develop perspiration and all sorts of 
eruptions: erythemata, urticaria, papules, vesicles, ulcera- 
tions, pemphigus. Antipyrin and most of the anti-pyretics, 
quinin, iodids, copaiba, arsenic, phenol, iodoform, animal 
serums, are the substances that most frequently produce 
eruptions; but there are many others liable to cause 
cutaneous manifestations, such as arsenic, rhubarb, chloral 
hydrate, opium, and tannin. 

The mucous membranes also are very sensitive to medicines : 
stomatitis (mercury), coryza and angina (iodids), medici- 
nal gastritis (all medicines administered too long), enteritis 
(repeated laxatives of drastic character) are often due to 
intolerance. 

The nervous system strongly reacts, at times in a very 
dramatic fashion, to substances acting upon it directly or 
indirectly: headache, vertigo, delirium, trembling, somno- 
lence, apathy, collapse, coma, convulsions, or anesthesia may 
result from the administration in too large doses of a great 
variety of medicines such as cafTein, digitalis, quinin, alcohol, 
all the antipyretics, salicylates, all the hypnotics, belladonna, 
opium, illy tolerated purgatives, emetics, etc. 

The alimentary canal manifests its intolerance by nausea, 
vomiting (morphin), colic and diarrhea (mercury, cod-liver 
oil, copaiba); the kidneys, by albuminuria (mercury), oli- 
guria or anuria (morphin, antipyrin, cantharides) ; the res- 
piratory organs, by dyspnoea (caffein), acceleration or slowing 
of respiration; the heart, by palpitation (caffein, spartein, 



ELEMENTS OF THERAPEUTIC INDIVIDUALIZATION 171 

phosphates), excessive slowness (digitalis), irregularity (id), 
cardiac collapse (all cardiac depressants, antipyretics . The 
blood expresses its intolerance by hemoglobinuria or hemato- 
porphyrinuria. The iodids sometimes affect the parotids, 
the larynx, the lungs, possibly the brain; the ferruginous 
preparations affect the bladder, etc. 

I have discussed at length in my "Traite de Therapeutique " 
the phenomena of intolerance in regard to each medicine, 
because the physician must know them very accurately to be 
able to distinguish between modifications that result from 
the disease and those which may be caused by a medicine. 

Repetition of the same medicine may impart to tolerance 
two reverse modifications: the strengthening of this aptitude 
by habituation, or else intolerance either by augmentation 
of the habitual reaction (hyperesthesia to medicinal action), 
or by accumulation. 

Medicinal habituation or assuetude is generally defined " toler- 
ance acquired by habit.' ' It makes it possible to tolerate, 
by an increasingly greater dosage, quantities which, if given 
in the beginning, would prove fatal or at least toxic. Thus, 
the subcutaneous injection of 1 grm. of morphin (fatal 
for a non-accustomed subject) is tolerated very well by many 
morphinomaniacs. 

To comprehend habituation we must bear in mind the 
adaptation of the living matter to environment. This is strik- 
ingly shown by the adaptation of amebae of sweet water to 
salt water, by means of successive passages into increasingly 
more concentrated saline solutions. With reference to me- 
dicinal substances this adaptation is realized in man as 
regards morphin, heroin, cocain, chloral, arsenic, coffee, 



172 PRINCIPLES OF THERAPEUTICS 

alcohol, atropin, ether, perhaps iodin and mercury, etc. 
From personal observation I believe it possible for digitalin. 1 

However, habituation is not always exactly "tolerance 
acquired by habit"; it is often a form of intoxication in the 
sense that, under its influence, the living matter has adopted 
a mode of reaction different from that of the healthy state. 
It may sometimes happen that the equilibrium and fixity of 
this living matter are no longer possible without the effect of 
the medicine. Hence, habituation often creates the urgent 
need of the same medicine, a need which leads to repetition 
and progressive increase of the doses, resulting in chronic 
intoxication. 

The state of intoxication sometimes reveals itself, for a 
long period of time, by the imperious need alone, but if the 
action of the toxic substance is continued for a long period 
the disturbance of normal metabolism results in lesions or 
decay. Thus a subject accustomed to a strong dose of al- 
cohol may have a crisis of delirium tremens if he suspends 
its use, but if he continues, he exposes himself to eventual 
nervous, cardio-vascular, renal, or hepatic disorders. A 
morphinomaniac deprived of morphin may present a fatal 
cardiac collapse, but if it is not suspended he is sure to de- 
velop morphinic cachexia and probable decay in the more 
or less remote future. 

Habituation, therefore, is not always a useful phenomenon; 
it becomes useful only when it secures tolerance for large 
doses of a medicine which must be given in large doses to 

*I refer to a patient who, during the last five years of his life, took every 
week, except for two interruptions of three months each, from 1 to 2 mg. 
of crystallized digitalin of Nativelle (from 50 to 105 drops of a 1 per 
thousandth solution). 



ELEMENTS OF THERAPEUTIC INDIVIDUALIZATION 173 

produce its curative effects. Thus it is possible, after habitu- 
ation, to administer iodid of potassium, mercury, or arsenic 
in doses which, if given at once, might cause serious trouble. 
But this habituation can be considered as neither certain 
nor definitive: phenomena of iodism or mercurialism may 
occur in the course of a treatment to which the patient seemed 
well accustomed. 

It is not always easy to account for the fact that tolerance 
gives way to intolerance, sometimes suddenly. In most 
instances it may be attributed either to accumulation of 
the medicine, 1 or to sudden failure in the ways of elimina- 
tion, or else to an intercurrent individual disposition, like 
menstruation in women. 

Habituation may result in medicinal inertia; this should 
be avoided. For this purpose, it is advisable not to give the 
same medicine for too long a period (see " Alternation," p. 
109), and not to spend much time in giving insufficient doses. 
The latter rule is especially important in etiocratic thera- 
peutics, since pathogenic agents probably undergo habitu- 
ation as do the elements of our own organs. It is therefore 
necessary vigorously to attack them as soon as possible. 
Small doses are to be given only for the purpose of ascertain- 
ing the tolerance of the patient; when this is established, 
the doses must rapidly be raised. 

Repetition of the same medicine may give rise to accu- 
mulation. There are two modes of this: accumulation of 
doses and accumulation of action. 

The doses are accumulated when they are stored up, with- 

1 Mercury, for example, may accumulate in the liver or in the subcuta- 
neous cellular tissue and be suddenly liberated into the circulation in too 
large quantities. 



174 PRINCIPLES OF THERAPEUTICS 

out being absorbed, at some point of the economy (digest- 
ive tract, subcutaneous cellular tissue, liver) later to be 
suddenly absorbed; hence, more or less grave toxic phe- 
nomena. Such phenomena have been observed with opium 
pills accumulated in the alimentary tract, but, above, all, 
with insoluble mercurial preparations injected into the sub- 
cutaneous cellular tissue. 

The accumulation of action results from persistence of 
the influence of previous doses beyond that of the following 
doses. When this is well managed, it is favorable, as it en- 
ables us to profit by several successive actions. Digitalis 
best enables us to observe this reinforcement of effects. The 
cure of most diseases amenable to specific treatment is ex- 
plained by this accumulation of successive actions. 

Fonssagrives distinguishes accumulation from medicinal 
erethism. The latter consists in an excess of reaction to a 
medicine unoler the influence of repetition of its action. This 
sort of hyperesthesia is quite rare. Nevertheless, it is some- 
times observed, especially in nervous subjects. There are 
some who, after having taken a certain quantity of quinin, 
can no longer tolerate the slightest dose of it without unbear- 
able tinnitus aurium. The repetition of certain medicines 
irritant to the stomach (iodics, chalybeates, copaiba) may at 
length produce such gastric disturbance as to necessitate 
their abandonment. The abuse of Vichy water sometimes 
causes alkalinity of the urine under the influence of a single 
glassful (Bouchard). Prolonged mercurial cures render 
many patients oversensitive to mercury: under the influence 
of small doses they then complain of nervousness, insomnia, 
and a painful state of depression. Other persons become 



ELEMENTS OF THERAPEUTIC INDIVIDUALIZATION 175 

intolerant for laxatives which they had tolerated well for 
some length of time. 

Many of these facts are accounted for by some appreciable 
organic modification, such as medicinal gastritis, enteritis 
produced by the abuse of laxatives; but many others have 
no known explanation. It is to these cases that the denom- 
ination medicinal erethism or hyperesthesia should be applied. 
Autosuggestion, or tiring of a medicine, may, in some in- 
stances, account for these excessive susceptibilities. The dis- 
tinction between these various states is not always possible, 
but the remedy imposes itself. Unless there should be 
pressing necessity, the patient should be relieved of the use 
of the medicine for a period sufficiently long to cause him 
to forget it, or else to replace it by a similar one. 



CHAPTER VIII 

INFLUENCE OF ENVIRONMENT ON THERAPEUTIC 

RESULTS 

Temperature — Light and color — Climate — Season — Ventilation — Fur- 
niture — Entourage — Nurse — Physician — Consultations — Change of Phy- 
sician — Pharmacist — Priest. 

Almost all the elements which compose the environment 
of a patient may exert a more or less marked influence on 
the development of the disease. They are composed of the 
temperature, light, color, climate, season, habitation, fur- 
niture, and entourage, some living more or less with the pa- 
tient (family, nurses, neighbors, friends), others seeing him 
more rarely (physicians, consultants, priests), or never seeing 
him (pharmacists). All these elements are worthy of at- 
tention. The word Oepairevoi means, properly, to serve; it is 
easily conceived that the therapeutist must overlook noth- 
ing that may serve the patient. 

TEMPERATURE 

The temperature at which a patient lives has an obvious 
influence on the gravity of many diseases. As a matter of 
principle, in acute states, an effort is made to guard the pa- 
tient against brutal thermal effects capable of exerting a dele- 
terious action on the great functions, particularly on the ner- 
vous system, the circulation, and the activity of the skin. 
When the action of cold water is resorted to, it is as an excep- 

176 



INFLUENCE OF ENVIRONMENT 177 

tional measure and dependent upon assured tolerance. It 
then becomes a question of a therapeutic procedure that 
has its indications and technic, and not a condition of 
environment. 

The optimum of temperature of the medium varies with 
the disease : a comparatively low temperature soothes typhoid 
fever. As far as possible it must not exceed 17° C. (62.6° F.); 
over 18° C. (64.4° F.) and especially 20° C. (68° F.), the pa- 
tient's temperature rises, the pulse is accelerated, insomnia 
and nervousness are produced or prolonged. It is necessary, 
on the other hand, to avoid intervention of sudden cold which 
may favor a dangerous pulmonary involvement. A moderate 
temperature of 17° to 18° C. (62.5° to 64.5° F.) is sufficient 
also for small-pox patients. In hemorrhage, there is an advan- 
tage in keeping the subject in a comparatively cool air, avoid- 
ing, at the same time, direct action of cold drafts. 

There is a group of diseases in which a uniform temperature 
of the medium is a matter of prime importance; such, for 
instance, is measles in its ordinary forms. A temperature of 
18° to 19° C. (64.4° to 66.2° F.) affords much chance to obviate 
its pulmonary complications. Acute affections of the res- 
piratory passages (pneumonia and broncho-pneumonia, bron- 
chitis, pleurisy), whooping cough at its onset, and acute articular 
rheumatism require the same condition. The steadiness of 
a comparatively high temperature (64° to 66° F.) is the best 
means of preventing the pulmonary complications of influenza. 
The occurrence of successive involvement in broncho-pneu- 
monia often coincides with exposure to the effect of cold. In 
all these cases the dominant indication is uniformity rather 
than elevation of the external temperature. 

12 



178 PRINCIPLES OF THERAPEUTICS 

In other diseases not only uniformity but a certain elevation 
of the external temperature is required: such are acute enter- 
itis and all diseases with a tendency to algidity (cholera, 
choleriform enteritis, certain grave forms of icterus, uremia). 

Subjects suffering from scarlet fever are not afraid of a 
little heat when their own temperature is not too high, while 
with hyperthermia they would feel better in a rather cool 
place. The steadiness of a somewhat high external tempera- 
ture (64° to 66° F.) helps to avoid streptococcic complications 
of scarlatina (glandular suppurations, otites, arthropathies, 
etc.); it is especially necessary when the fever has fallen, 
from the fifth to the thirtieth day and over, in order to avoid 
the nephritis due to the streptococcus which so readily develops 
in the kidneys of scarlatina patients under the influence of 
cold or of dietetic errors. 

In chronic diseases the influence of external temperature 
is no less important: chloro-anemia, syphilis, chronic enteritis, 
scrofulides, chronic affections of the mucous membrane of the 
respiratory passages, chronic rheumatism, chronic nephrites 
require a rather high and dry temperature. A moderate tem- 
perature with a little humidity is suitable for the nervous, 
especially if they do not sleep well, for dyspeptics, eczematic, 
and cardiac subjects. High temperatures are particularly 
unfavorable to cardiac cases: they fatigue the heart by 
imposing upon it an enormous labor for rapidly renewing the 
blood at the periphery of the body in view of its cooling. 

The tuberculous accommodate themselves fairly well to all 
temperatures not extreme, even to cold, provided they be 
guarded against it. What is most harmful to them is too 
high temperatures and the effects of abrupt variations. It is 



INFLUENCE OF ENVIRONMENT 179 

necessary to protect them from these variations by means of 
devices of clothing, habitation, and heating. 

LIGHT AND COLOR 

That red light in a certain measure prevents suppuration 
of the pustules of small-pox is no longer denied by anyone. 
It is credited also with a favorable influence on the develop- 
ment of scarlatina, measles and acute eczema. On the other 
hand, it is exciting and sometimes very fatiguing. Red light 
seems to be suitable for some melancholies; blue, on the 
contrary, is favorable to the agitated. Without exaggerating 
the importance of these color conditions, it is necessary to 
take them into account. 

There is no doubt that semi-darkness promotes rest in acute 
diseases, and that, on the contrary, light is favorable in chronic 
maladies. 

CLIMATE AND SEASON 

The effects of medicines are not absolutely the same in 
all countries and at all reasons. Hot seasons and hot coun- 
tries, cold seasons and cold countries present notable analo- 
gies. Alcohol, in non-toxic doses, is far better borne in the 
north than in the south, in winter than in summer. Ex- 
perimentally a slightly high temperature lessens the dangers 
of alcohol in toxic doses. Tartar emetic, in contrastimulant 
doses, has at all times been considered as contraindicated 
in very cold and in very hot weather. 

It seems a priori that the physiological modifications ex- 
erted by climate or season emphasize those produced in the 
same direction by a medicine, and attenuate those of a reverse 



180 PRINCIPLES OF THERAPEUTICS 

character. Hence the rule of avoiding remedies that are 
liable to depress in depressing seasons and climates and of 
fearing the excitants under reverse environmental condi- 
tions. But this principle remains a priori: we are not yet 
in possession of facts enabling us to apply it with precision. 
Several patients have told me that they have iodism more 
readily in Riviera than at Paris. I cannot tell whether the 
observation is correct. It seems that many of the contra- 
dictory assertions touching the effects of medicines, particu- 
larly of diuretics and hypnotics, are due, in part, to the di- 
verse influences of countries where the observations have 
been taken. The variable reactions of races also should be 
taken into account. Notable differences in the medicinal 
potency of plants according to their countries of origin (aco- 
nite, digitalis) account for a certain number of differences 
noted in the action of medicines in different countries. Of 
course, climate and season (as well as race) have a notable 
influence on the gravity of diseases: typhoid is graver in hot 
than in temperate climates, in summer than in winter. Con- 
versely, scarlatina is graver in winter than in summer, in 
England than in France. 

It is probable that medicinal effect produces a somewhat 
variable reaction according to the temperature of the medium; 
but these variations are not known to us except in regard to 
extreme temperatures and a few medicines. In a general 
manner it may be said that actions are added : thus an Organism 
depressed by cold or extreme heat may be gravely impressed 
by the abrupt action of alcohol; but these extreme cases are 
but seldom realized in therapeutic practice. It has been 
noted, however, that diuresis is more readily produced in 



INFLUENCE OF ENVIRONMENT 181 

winter or by cold, and perspiration in summer or in a warm 
place. Certain subjects are highly sensitive to the surround- 
ing temperature, in regard to their predisposition to sleep, 
digestion, and intestinal freedom. Many dermatoses are 
cured with difficulty in a cold medium, and yet eczema is 
often exasperated during the hot season. Under these vari- 
ous conditions therapeutic action loses some of its usual 
efficacy. 

VENTILATION 

The air in a patient's room is rapidly used and charged 
with odorous emanations and foreign bodies. It is there- 
fore indispensable to ensure ventilation without causing 
the patient any inconvenience, and in accordance with what 
already has been said when treating of the requirements of 
the patient in regard to external temperature. 

FURNITURE 

Hygiene advises that there be nothing useless in a patient's 
room and that everything may be subjected to disinfection 
if necessary; and therapeuties requires the easy removal of 
air immediately surrounding the patient. Nothing is more 
uncomfortable and injurious for a feverish and particularly 
a hyperpyretic patient than to live in vitiated air. The air 
should incessantly abstract some heat by its passage through 
the respiratory organs and even on contact with the skin. 
The bed should always be placed a certain distance from the 
walls, in order to permit the air freely to circulate around it. 
This arrangement secures comfort and often a reduction in 
temperature in the feverish, especially in children. Anything 



182 PRINCIPLES OF THERAPEUTICS 

which impedes the circulation of air in the sick-roorn must 
be done away with. In order, however, that this circulation 
may not be violent and may not disturb the steadiness of 
temperature, it may, in some cases, be necessary to modify 
and control it by means of screens. The bed should always 
be placed in such a manner that the light may not directly 
strike the patient's eyes; thus sleep and rest are facilitated. 

ENTOURAGE 

The influence of environment on the action of certain reme- 
dies is of prime importance: hypnotics do not act satisfac- 
torily except in silence. Calm and comparative isolation of 
the patient are often indispensable conditions for the thera- 
peutic action of medicines. Conversely, certain nervous 
subjects feel apprehension if they have nobody to observe 

them and help them when in need. These circumstances 

- 

therefore dictate the rule that, if a patient is not to remain 
completely isolated, his entourage must not be numerous and 
noisy and a curiously observing one, talking with more or less 
discretion, passing judgment on everything and engendering 
fatigue and sometimes even disquietude. In certain circles 
people believe they manifest interest for the patient by over- 
burdening him with solicitous demonstrations. In all febrile 
and important diseases such demonstrations are injurious. 

NURSE 

Nurses play a considerable part in the treatment of a great 
many diseases. Clean, trained, disciplined, silent nurses 
render the most indispensable service, aid the physician's 
observations and ensure the execution, often more delicate 



INFLUENCE OF ENVIRONMENT 183 

than the prescription, of difficult therapeutic measures, such 
as cold bathing in typhoid fever. If unclean, ignorant, noisy, 
and pretentious, they do great harm. The pitfall of nurses is 
lack of modesty. There are those who dare to correct the 
physician's diagnosis or criticize the treatment they are to 
carry out. Many have a notion that the doctor does not 
purge enough; they therefore give enemata or increase the 
dose of laxatives — a dangerous conduct in many cases (ap- 
pendicitis, typhoid, enteritis, etc.). How often is she the 
cause of a useless consultation, and how often does she 
undermine the confidence of the patient in his physician! 

The function of a nurse should be trusted only to those who 
have received sufficient technical instruction and had hospital 
experience. The qualified nurse should, of course, be liber- 
ally remunerated. The larger the nurse's salary, the more 
enlightened care and better habits of a good education may 
be demanded of her. 

It is necessary that nurses and in general all persons who 
take care of a patient should get sufficient rest. From ex- 
cessive zeal or affection to devote oneself too unsparingly to 
the patient is harmful both to the attendant and the 
patient: fatigue engenders lack of precison, relaxation in 
hygienic care, irritability, forgetfulness, a disposition to 
disease, all of which are obviously undesirable and some- 
times highly prejudicial. 

It is hardly necessary to say that the physician must see 
that the attendants do not uselessly expose themselves to the 
contagion and that they observe all prophylactic measures 
indicated (special clothing, washing, preventive serums, 
abstention from all useless promiscuity, etc.). 



184 PRINCIPLES OF THERAPEUTICS 



PHYSICIAN 

The r6le of the physician is naturally the most important. 
It is at times the least recognized. I mean that the physi- 
cian's service is not always fully appreciated. He is too 
often judged from every point of view except that of medicine, 
which is natural enough, since his judges have no knowl- 
edge for medically appreciating him with certainty. The 
choice and authority of a physician depend upon his official 
position, reputation, and the sympathy he inspires by his 
speech, manners, diplomacy, and, above all, his authority. 
The public has no way of judging the value of his methods 
except by instinct and by the results perceptible to the senses. 
But these results are valued according to the idea formed in 
advance, namely, the diagnosis, which is the most difficult 
part of medicine. 

It is readily conceivable to what errors of interpretation 
the prognosis of the public would lead. Therefore, without 
fear of being parodoxical, we may say that a physician who 
is really well educated and a good therapeutist, but who 
lacks diplomacy, will not readily succeed. Such a man, 
in fact, will never make miraculous cures. Seldom mak- 
ing any mistake in diagnosis and generally formulating a 
right prognosis, he cannot pass for a great healer: the cure 
announced by him as probable will always be considered as 
natural, and it will always be counted a failure not to 
prevent death, even when the prognosis is of the gravest 
character. 



INFLUENCE OF ENVIRONMENT 185 

How much more brilliant is the physician who, less thor- 
oughly equipped, is as uneasy and astonished as the family 
in the presence of a common phenomenon, such as a high 
temperature, until defervescence, natural or otherwise, justi- 
fies the medication employed and gives rise to lasting grati- 
tude for the savior! How often a sore throat, which is non- 
diphtheritic but presented as such by an error of diagnosis, 
has caused the grateful admiration of the family, while the 
experienced physician who, within twenty-four hours, has 
made an injection of antitoxin, is coldly thanked for his task 
the following day and perhaps even suspected of having 
wrongly alarmed the family, because the cure is secured too 
easily. How often a physician is credited with having aborted 
a typhoid fever that was nothing more than a somewhat 
prolonged influenza or a gastro-enteritic infection of no 
gravity! Here is a physician who practises catheterism 
in strict accordance with the rules of asepsis, there is no reason 
why he should be praised beyond measure for having done 
so simple a thing. But another physician will infect the 
urinary passages and produce a violent paroxysm of fever 
which will never be suspected by the entourage to be ascrib- 
able to a manoeuvre so simple as the introduction of a sound; 
he will nevertheless benefit by the cure of the fever and even 
be considered an able practitioner. The learned physician 
should not mind the unjust judgments of a public that lacks 
the criterium of good therapeutics: his conscience and the 
satisfaction of having been an honest as well as an expert 
practitioner of his art, even if he should remain obscure, will 
amply reward him for the unjust judgment of incompetent 
people. But the physician in charge is not always alone 



186 PRINCIPLES OF THERAPEUTICS 

in influencing the treatment of a patient: there is often the 
intervention of another practitioner to be taken into ac- 
count, either in the way of consultation or because the pa- 
tient or those interested in him, dissatisfied, distrustful, or 
ill-advised, have changed their physician; therapeutics is 
always modified thereby. 

CONSULTATIONS 

Leaving aside the viewpoint of medical ethics, I shall call 
attention to the therapeutic consequences of consultations, 
which may be good, bad, or indifferent. 

A consultation can have no useful therapeutic effect when 
a consultant is called in to cover a responsibility in extremis, 
or even when the patient's life is definitely endangered, or in 
the course of an incurable disease approaching its termina- 
tion, or, lastly, when the value of the consultant is too far 
below that, of the physician in charge. In these various cases 
consultation is a mere formality or a satisfaction given to 
the family or the physician. Neither can anything be ex- 
pected therefrom in cases when the treating physician, placed 
face to face with a consultant, feels certain that his 
diagnosis is correct and that his therapeutic scheme is the 
best that science is capable of inspiring. In such a state of 
mind consultation becomes a useless conversation and the 
attempt to change his opinion is generally superfluous. 

A consultation can have a favorable therapeutic effect 
only when the physicians, free from personal considerations 
and prejudices, conscientiously look after the patient's inter- 
ests, especially if his condition is giving rise to difficulties. 
Moreover, it is necessary that the physicians agree on all the 



INFLUENCE OF ENVIRONMENT 187 

points of the treatment and its subsequent course, since noth- 
ing would be more detrimental than a merely approximative 
direction representing no definite practice which would em- 
barrass the physician intrusted with its execution. 

A consultation may have regrettable consequences when 
the consultant makes a mistake, when he is incompetent, 
or when his advice, though wise, is not accepted. A consult- 
ing physician, even a learned one, may err, for the sufficient 
reason that, having seen the patient but once, he cannot 
know his various reactions as accurately as the attending 
physician. The latter, at times somewhat humiliated under 
the circumstances, cannot always make acceptable his well- 
founded objections: out of two good wills, both conscientious 
and thoughtful, may come a practical error as a conse- 
quence of the preponderating part played by the physician 
whose knowledge of the patient is less thorough. 

At other times the consulting physician is one of those men 
who, through their diplomacy, greater than their science, have 
acquired the undeserved reputation of exceptional excellence. 
As a matter of course, he considers the confrere as an inferior. 
He starts by reforming the latter' s diagnosis without suspect- 
ing that in most cases he is substituting an error for a reality. 
Next, he proposes a new treatment. In case of recovery, he 
is credited with the success; in case of failure, his reputation 
saves him. 

In other cases, the attending physician has known, by his 
manners, how to win the confidence of the patient and his 
entourage. Having thus rendered his position unassail- 
able, it is he who, in a case that does not improve, requests 
a consultant. Everything is correct in appearance : the consult- 



188 PRINCIPLES OF THERAPEUTICS 

ant is very cordially welcomed; he is listened to with defer- 
ence; his advice is written down; they bid each other farewell 
with warm words of courtesy, and, on the following day, with- 
out taking into account his advice, another consultant is re- 
sorted to. Sometimes as many as a dozen are thus success- 
ively called until one is found who proves to be of the same 
opinion as the attending physician and ratifies his failure or 
who, by force of repetition of the same advice, has the good 
fortune to arouse salutary reflections and to be listened to. 

The therapeutic role of the consultant is usually a very 
easy one. He generally intervenes at a moment when, the 
disease no longer being at its beginning, diagnosis is facilitated. 
He can profit by the observations which the attending phy- 
sician has had time to make. If the malady is grave, he is 
not blamed for it; if benign, he participates in the credit of 
the cure. The consultant, apart from his technical value, 
needs three qualifications for rendering the greatest services : 
conscience, modesty, and professional honesty toward his 
confrere. Conscientious, he studies with the attending physi- 
cian the difficult cases without haughtiness and without abso- 
lutism; modest, he listens to the attending physician and con- 
siders his observations and objections; fraternal, he avoids, 
in the presence of a grave disease, undue optimism which 
would place the family physician in a difficult position in 
regard to the progress of the malady. 

As to the attending physician, protected against exaggerated 
responsibility by the consultant's intervention, he must also 
be conscientious and modest: conscientious, he listens impar- 
tially to all the observations that may be made; modest, he 
does not obstinately adhere to a possible error, and achieves 



INFLUENCE OF ENVIRONMENT 189 

an honorable step in the direction of truth which he has recog- 
nized, Nothing is easier in practice. 

CHANGE OF PHYSICIAN 

The course of a disease is often modified by the change of 
physician. Patients suffering from an acute disease some- 
times grow worse as a result of this change, while those af- 
flicted with a chronic disease are often benefited thereby. 
This observation may readily be verified in hospital wards at 
the time when the consulting physician is changed. Probably it 
is not advisable to modify too much the manner of being of 
a patient in the course of an acute malady. However, there 
may be some beneficial suppression of medicines to be made. 
I have seen the cessation of delirium by the suspension of 
large doses of caffein, and the disorderly agitation of the heart 
by that of aconite. But such cases are rare, and it seems to 
me that, as a matter of principle, it is not well, from any point 
of view, abruptly to change the general conduct adhered to 
by a predecessor. It is simply necessary to see whether there 
is any suppression to be made of a medicine which no longer 
is indicated, or which has been taken long enough, or which 
gives rise to phenomena of intolerance. 

On the other hand, in chronic diseases, the treatment to 
which the patient is accustomed sometimes no longer produces 
any effect. It may also happen that the physician, accus- 
tomed always to see the same patient, tends to confine him- 
self to the observation of disturbances the development of 
which he has seen, and it is possible that, though atten- 
tive, he does not perceive the slow and insidious establish- 
ment of additional disorders which do not arrest his atten- 



190 PRINCIPLES OF THERAPEUTICS 

tion. The new physician cannot understand how these 
disturbances have escaped attention: a little albumin or 
even pus in the urine, or a recent glycosuria, for in- 
stance. A physician must be indulgent when he has not 
witnessed the evolution of morbid states, and especially, in 
those cases where one is unable to see the reasons for 
an error; however, it is certain that the revelation of a new 
fact may become the source of indications beneficial to the 
patient. 

Conversely, the change of physician may sometimes have 
regrettable consequences in chronic cases: this may happen 
in the course of an incurable disease to which the patient can- 
not become resigned. He changes physicians until he finds 
one who promises to cure him. These successive trials often 
cost him his life. Three times in the course of a year I have 
seen the end of patients under these conditions. All three 
were suffering from Bright's disease attended by dyspnoea. 
Tired of a hygienic treatment which conferred nothing but a 
modus vivendi without any other issue than death more or 
less distant, they sought recovery outside of hygienic arrange- 
ments and cessation of the symptom dyspnoea through me- 
dicinal action. Two of them were treated with morphin, 
which is advised in these cases by eminent practitioners, with 
whom, however, I do not agree in this respect. At first these 
patients breathed better; but soon the kidneys were ob- 
structed, oedema made rapid strides, and in less than two 
months both died. The third was treated with an inten- 
sive iodic medication which seemed to succeed at first; but, 
at the end of a few weeks, a pulmonary complication ap- 
peared which carried off the patient. 



INFLUENCE OF ENVIRONMENT 191 

In the presence of an incurable affection the physician 
must try, either personally or through well-chosen consult- 
ants, to explain to the patient, and particularly to his entour- 
age, that a sufficiently long existence is still possible for 
him with a given mode of life; i.e., provided his physical ac- 
tivity be adjusted to his forces, his diet to the capacity of 
his digestive organs and to the powers of depuration; but 
that to seek recovery by means of active medicines would 
be a mistake liable to cost him his life. In carrying out this 
fastidious and deceiving program, the influence of the entour- 
age is considerable, since it is the entourage that sustains 
confidence or engenders distrust. The physician is obliged 
to take it into consideration. 

PHARMACIST 

An important part of therapeutic successes is due to the 
pharmacist. There is no good therapeutics without good 
pharmacists. The most judicious prescription would fail 
if the medicine delivered were impure or in wrong dosage 
or if the preparation were defective. 

PRIEST 

In the Roman Catholic religion it is customary for a priest 
to assist his coreligionists before death. The arrival of 
the priest is, therefore, for many people who profess very 
little, if any, religion, the official announcement of an ap- 
proaching end, so much feared by most men of our race and 
of our moral education. This is to say that the priest's in- 
tervention is by no means a negligible event from the stand- 



192 PRINCIPLES OF THERAPEUTICS 

point of its influence on the physical state of the patient as 
well as on his moral tranquility. 

As a matter of principle, the physician's attitude in re- 
gard to religious practices should be neutral; he must not 
intervene except when he perceives an undesirable pressure 
exercised upon the patient. Even when he is consulted by 
the family he should not go beyond the simple expression 
of a probable and always reserved prognosis. His medical 
quality authorizes him to add his opinion as to the favor- 
able, indifferent, or undesirable consequences of the inter- 
vention of a priest. In some cases he will not be able to es- 
cape from the obligation of expressing his opinion; he will 
then strive to harmonize the fundamental principle of the 
respect due to the patient's opinions, as well as his quietude 
and the scruples of the family. 

When a sincerely religious patient desires a priest, there 
is advantage in f giving him satisfaction, since his nervous 
dynamism will certainly he enhanced by the fulfilment of 
a duty dear to his heart and by the quietude resulting 
therefrom. 

If the patient is indifferent to religion and the priest's as- 
sistance is regarded by him and his family as a mere for- 
mality, the physician must be very reserved and quite sure 
that this intervention will have no harmful influence upon 
the development of the malady. To this effect, it is proper to 
wait, in order to give an approbative opinion, until prognosis 
becomes definitely hopeless. 



CHAPTER IX 

VARIATIONS OF THERAPEUTIC ACTIVITY INHERENT IN 

MEDICINES AND THEIR MODE OF 

ADMINISTRATION 

Causes of variation in the activity of substances on the organism — 
Physical properties — Ionic dissociation — Chemical structure — Active prin- 
ciples — Incompatibilities — Specialties — Subcutaneous and intravenous in- 
jection — Fractional dosage and alternation. 

The causes capable of modifying the activity of a sub- 
stance on the organism are innumerable. Some, directly 
dependent upon the mode of employment of remedies, must 
be minutely known to the practitioner; others, related to 
the physical properties of matter or to the chemical struc- 
ture of medicines, do not constitute, from a practical stand- 
point, a matter of indispensable knowledge; it is well, how- 
ever, not to overlook them, in order to be able correctly to 
judge the statements of promoters of new remedies and to 
avoid the risk of formulating hypotheses which may be shown 
to be without any ground in physico-chemical sciences. 

In the methodic table below we give the principal causes of 
variations in medicinal activity inherent in medicines; we 
shall lay stress on the most important and the least known 
among them. 

I. Variations of activity inherent in the therapeutic 

AGENT. 

A. According to its state and physical properties: Solubility; 
concentration; state of mechanical division; diffusibility; 
temperature; degree of dissociation. 
13 193. 



194 PRINCIPLES OF THERAPEUTICS 

B. According to its chemical composition: Chemical struc- 
ture; proportion of active basis; added action of components. 

C. According to pharmaceutic preparation: Active principles; 
galenic preparations; country of origin; solutions; powders; 
wafers; gelloids; compressed tablets; dragees; capsules; 
pills; granules; associations; nature of excipient; specialties; 
asepsis of preparations. 

II. Variations of activity inherent in mode of admin- 
istration. 

A. According to the routes of introduction into the organism: 
Subcutaneous, intramuscular, and intravenous injections; in- 
gestion; enemata; absorption by the skin, respiratory pas- 
sages, wounds, and the mucous membrane; intraspinal in- 
jection. 

B. According to the divisions of doses: Massive doses: 
fractional doses; alternation. 

VARIATIONS OF ACTIVITY DERIVED FROM THE PHYS- 
ICAL PROPERTIES OF MEDICINES 

We shall briefly point out the well-known variations which, 
due to the physical state of medicines, are related to their 
degree of solubility, concentration, mechanical division, diffu- 
sibility and temperature. 

Solubility; Concentration. — As a rule, the more soluble 
a body and the more concentrated the solution, the greater 
is its activity; but activity means neither utility nor efficacy. 
Certain very irritant and consequently very active substances, 
in concentrated solution, are non-utilizable in that state, but 
become very useful in a diluted solution, such are purgative 
salts, bicarbonate and salicylate of soda, iodin, etc. Calomel, 



VARIATIONS OF THERAPEUTIC ACTIVITY 195 

in intramuscular injection, although insoluble at the time of 
its administration, is more efficacious than soluble mercurial 
preparations in the treatment of syphilis. Intestinal anti- 
septics can fulfil their function only when they are slowly 
and hardly soluble (benzonaphthol, salacetol, etannigen). 
There are even some substances, such as subnitrate of bismuth, 
which act just because they are insoluble. 

State of Mechanical Division. — On the other hand, the 
extreme division of a powder is a condition of activity and 
efficacy, either because it facilitates the necessary solubili- 
zation (sulphonal, trional), or because it favors the mechanical 
action (subnitrate of bismuth). 

Diffusibility. — The rapidity of absorption and elimination 
of a fluid is directly proportional to the rapidity of its diffu- 
sion. This is, however, only a general rule. Certain medi- 
cines, like the iodids, in spite of their rapid diffusion, remain 
for quite a long time in the economy, perhaps because that 
part which is eliminated by the digestive organs (salivary 
glands in the case of an iodid) is reabsorbed. For some un- 
known reasons, highly volatile and highly diffusible sub 
stances, when taken to excess, may be retained within cer- 
tain organs: thus alcohol remains for a long time in the 
brain and the liver. 

Temperature. — It is not an indifferent matter to leave 
the temperature of a medicinal or hygienic drink to the pa- 
tient's judgment. The temperature may be turned to benefit. 
Moderately warm drinks attenuate the reflexes and secre- 
tion of the stomach, hence their utilization in hyperchlor- 
hydria and spasm of the pylorus; they facilitate the solution 
of certain substances ingested in a solid form (sulphonal, 



196 PRINCIPLES OF THERAPEUTICS 

for instance); they soothe cough, promote perspiration. On 
the contrary, cold beverages excite the stomach and favor 
diuresis. It is for the latter reason that preference is given 
to cold drinks in hyperpyrexias which demand the maintain- 
ance of an active diuresis (typhoid fever). Conversely, warm 
drinks are prescribed in diseases requiring a uniform temper- 
ature (measles, pneumonia, influenza, sometimes scarlatina). 
Ice drinks soothe nausea and cause contraction of the per- 
ipheral blood-vessels, utilizable in certain hemorrhages; they 
also stimulate the hydrochloric secretion of the stomach. 

According to Dr. Linossier's experimentation, tepid water 
(100° F.) is less exciting to the stomach than hot water (136° 
to 140° F.) or cool water (53° F.). 

According to Sassesky, hot solutions are more readily ab- 
sorbed than cold, not only by the rectum and the subcuta- 
neous cellular tissue, but also by the stomach. 

Electrolytic or Ionic Dissociation. — This particular 
state of molecules has recently been credited with a great 
part in toxic and medicinal activity. Its importance may 
have been exaggerated, or at least the demonstration of this 
importance has not been complete. However, in view of its 
actuality, I shall present the principal terms of the question. 

Let it be noted first that there is a parallelism between 
the physical properties dependent upon the number of mole- 
cules in a solution, as much from the standpoint of osmotic 
pressure and tension of vapor as from the standpoint of 
congelation (freezing). The study of the latter being familiar 
to physicians, it alone will be considered here. Conclusions 
would be the same in examining the question from the other 
view-points. 



VARIATIONS OF THERAPEUTIC ACTIVITY 197 

It has long been known that solution of substances in water 
lowers the freezing-point of this liquid. M. Ptaoult has shown 
this to be true no matter what the solvent may be. The 
degree of lowering is not submitted to any single law; two 
cases may be considered: 1. non-electrolytic solutions, viz., 
those that do not conduct electricity (sugar, urea, acetic acid, 
albumen); 2. electrolytic solutions which conduct electricity 
(aqueous solutions of salts, strong acids, strong bases). 

There results from M. Raoult's researches that lowering 
of the freezing-point of dissolved non-electrolytic bodies is 
independent of the nature of the body dissolved and of the 
nature of the solvent; it depends only upon the number of 
molecules of both of them, and is proportional to the number 
of molecules dissolved. But in the case of solutions conduct- 
ing electricity (electrolytes), the lowering of the point of 
congelation is greater than anticipated by calculation, accord- 
ing to the number of molecules, and varies in notable pro- 
portions according to the salt in solution. 

In order to explain this exception to the general law, several 
hypotheses have been advanced; the one most favored is that 
of Swante Arrhenius (1887), according to which a certain 
number of molecules in electrolytic solutions are sponta- 
neously dissociated, owing to the very fact of the dissolution 
in water, into fragments which concur, as entire molecules, 
to lower the freezing-point. These supposedly free molecu- 
lar fragments have heen called ions, being likened to the ele- 
ments liberated at the electrodes when an electric current tra- 
verses a solution of a salt in water (iw traveller). These dis- 
sociated molecular fragments should be considered as atoms 
cr more or less complex groups of atoms (radicals). Their 



198 PRINCIPLES OF THERAPEUTICS 

liberation does not depend upon the passage of a current; 
it results from the very fact of solution in water, and renders 
the solution electrolytic, that is, it permits the passage of 
the electrical current, the latter being precisely transported 
by the ions. 

The dissociated ions present a peculiar state, they remain 
isolated and have no tendency to combine so long as they 
have an electric charge, which has led to the supposition 
(Nerntz) that this electric charge satisfies their affinity. 

Arrhenius's theory has given rise to contradictions (Chrou- 
stchorT, Ponsot, Reychler). It has been opposed by the 
theory of modules which involves the nature of bodies in the 
explanation of the lowering of the point of congelation, and 
by that of monads, according to which the ions are not free 
in electrolytic solutions: the salts in solution are divided 
into two physical molecules or monads, one basic, the other 
acid, which, although exactly neutralizing each other, have 
each an influence on the reduction of the congelation point: 
NaCl + H 2 0=NaOH + HCl. 

Whatever the exact nature of the solution taking place 
within electrolytic solutions, it is certain that a phenomenon 
of dissociation intervenes and that medicinal activity is 
notably modified, according to the degree of this dissociation. 

Here are a few illustrations given by Prof. Leduc 
(of Nantes): phenol, very caustic in a 5 per cent, aqueous 
solution, is no longer so in the same percentage of vaselin 
or glycerin, because, according to M. Leduc, these solutions 
not conducting electricity, the dissolution is not manifested 
and the ionic effects are suppressed. Even chemical, toxic, 
and remedial actions are proportional to the number of ions 



VARIATIONS OF THERAPEUTIC ACTIVITY 199 

in a given volume, viz., solely depend on the degree of dis- 
sociation. Thus, strong acids are very much dissociated 
and weak ones very little. Mercury salts with organic acids 
are far less toxic than bichlorid of mercury, because the 
former are not dissociated at all or form parts of complex 
ions, while in solutions of bichlorid the degree of dissocia- 
tion is very marked. In fact the complexity of ions must 
be taken into account. By entering into a complex ion, 
atoms completely change their properties. Complex ions 
are far less active than simpler ones. Thus, for instance, 
phosphids owing to the phosphorous ion have a great tox- 
icity, while phosphates are quite inoffensive, because, in the 
latter, phosphorus is part of a complex ion. Similarly, in 
cacodylates, arsenic is part of a complex ion in which it loses 
its fundamental properties. We may also mention the ex- 
periments of Paul and Kroenig (1896-1897) demonstrating 
that the antiseptic action of mercury salts, containing the 
same proportion of metal, is variable and directly propor- 
tional to their degree of dissociation. 

It is at present impossible to foretell the therapeutic con- 
sequences of the idea of dissociation of molecules in aqueous 
solutions. It explains for the time being that water inter- 
venes to impart a great activity to substances which are 
better tolerated in other vehicles. 

VARIATIONS OF ACTIVITY DERIVED FROM THE 
CHEMICAL COMPOSITION OF MEDICINES 

Chemical Structure. — The influence of the chemical 
structure of medicinal chemical compounds is more im- 
portant from the view-point of creators of new remedies than 



200 PRINCIPLES OF THERAPEUTICS 

from that of the practitioner. The latter should note, first 
of all, that in practice there is no certain conclusion to be de- 
rived from the chemical structure of a substance. There may 
exist probabilities which may change into certainties after 
experimental researches. In no case can the chemical struc- 
ture of a substance be considered as sufficient to warrant 
a clinical application as a first test. With this reservation, 
it has been possible to recognize a certain number of useful 
general ideas. 

As always, in therapeutics, those notions which have 
assumed the form of a law have proved untrue. Thus 
Blake, and then Rabuteau had asserted that the greater the 
atomic weight of a metal, the greater its activity. The comparison 
of the salts of sodium, a metal whose atomic weight is 23, 
and the salts of potassium, a metal whose atomic weight 
is 39, seemed to lend reason to this so-called law. But 
the law is deficient if we consider lithium, whose atomic 
weight is only 7, and which is nevertheless highly toxic 
(Husemann, Ch. Richet). Ch. Richet concludes from his 
experimentations on the chlorids, bromids, and iodis of 
lithium, potassium, and rubidium, that it is the molecular 
weight, not the atomic, that is important. But, as is 
judiciously observed by Stokvis, these attempts will re- 
main unfruitful as long as the absolute identity of the inti- 
mate process which causes death has not been established 
in regard to all these substances. How is it possible, in fact, 
to compare with one another substances which do not affect 
exactly the same organs? The fact is that when experiments 
have been made in this direction, i.e., on an identical tissue, 
no relation has been demonstrated either as regards the 






VARIATIONS OF THERAPEUTIC ACTIVITY 201 

atomic or the molecular weight (experiments of Lauder 
Brunton, of Binet). We must, therefore, guard against so- 
called laws governing therapeutics: the complexity of this 
science has hitherto defied all attempts at generalization 
and systematization. 

This does not mean that there is nothing interesting to 
know about the relations between the chemical constitution 
of medicinal substances and their therapeutic action. On 
the contrary, in most cases, all compounds which derive their 
activity from the same substance possess properties more 
or less similar: thus the various quinin salts, and those of 
mercury have analogous effects, though there is no absolute 
identity of activity. Especially in the domain of organic 
chemistry the molecular structure exerts a manifest influence 
on medicinal activity. The intoxicating properties com- 
mon 'to monoatomic alcohols of the fat series (methylic, ethylic, 
propylic, etc.), the antiseptic potency of 'phenols, the 
antithermic properties of quinolin derivatives, the purging 
properties of a great number of quinons, demonstrate that 
chemical compounds of analogous constitution present a com- 
parable physiological action. Take, furthermore, the methyl 
group, CH 3 ; its presence in the chain of a body of the aro- 
matic .series imparts to this body analgesic properties (Bardet). 
The radical ethyl, C 2 H 5 , possesses a hypnotic action which 
it conveys to various combinations. Thus the hypnotic 
power of sulphone derivatives is greater in proportion to the 
number of the ethyl group which they comprise : sulphonal 
comprises two; trional, more active, comprises three; tet- 
ronal, still more active but also more dangerous, possesses 
four. 



202 PRINCIPLES OF THERAPEUTICS 

However, the exceptions are so numerous that a knowledge 
of the chemical structure of medicines has but a very re- 
stricted value for the practitioner. Every change, even minute, 
in this structure, may give rise to important modifications in 
the physiological action. Thus it may happen that homologous 
bodies have quite different properties: cocain, for instance, 
possesses remarkable analgesic power; but among its homo- 
logues, there are some which are utterly devoid of this power 
and others that are violent cardiac poisons. Moreover, iso- 
meric substances may present considerable differences of 
both activity and physiological action. These differences 
may be determined sometimes by isomerics of position, at 
other times by stereochemical isomerics, viz., those in which 
the groupings constituting the molecule differ in their posi- 
tion in the space. 

Proportion of Active Basis. — Explanations of these 

*■ 

differences abound, but none has hitherto enabled us to fore- 
see with certainty the physiological action of a chemical sub- 
stance. More important for the practitioner seems to be 
the application which can be made of the knowledge of pro- 
portions of the active basis contained in a salt. Errors 
relative to this question oblige us to make a few additional 
remarks. 

First of all, it is admitted that quinin salts are active in 
proportion to the quinin they contain. This must be true 
in view of the reasons I will refer to later on. However, it 
must be noted that this is an a priori notion very difficult to 
demonstrate. Let us compare, in fact, the two salts most 
employed: the basic sulphate of quinin (the old neutral 
sulphate) which contains 0.743 grm. of quinin per gram and 



VARIATIONS OF THERAPEUTIC ACTIVITY 203 

the basic hydrochlorate which contains 0.817 of a gram. 
This comparison shows us a difference of 0.074 per gram, 
absolutely negligible for small doses (smaller than 0.60, for 
example) and of little importance for large doses of 0.80 to 
1.00 grm. The difference is only 0.022 per gram with the 
basic hydrobromate and 0.017 with the valerianate. Truly, 
for a compound whose posology is as elastic as that of quinin, 
the quantitative differences of the active base of the most 
usual salts are practically negligible. 

Many physicians have adopted the basic hydrochlorate of 
quinin on account of two considerations of a theoretical order: 
1. The hydrochlorate containing more quinin should be more 
active. We have just seen the doubtful importance of this 
argument; it is of no value when it is remembered that it is 
always possible accurately to give the desirable quantity of 
quinin by raising the doses. 2. The hydrochlorate is more 
soluble. This is true in vitro and in water, but in the acid 
medium of the stomach the difference becomes negligible. 
For my part, I prefer the sulphate. I have treated with this 
medicine a great number of malaria cases, not only of Algeria, 
but also of Tonkin, of Dahomey, and of Madagascar; I have 
not yet found sufficient reasons for abandoning the same. 
Nevertheless, one may argue with some probability (though 
without conclusive evidence) that the salts of organic bases 
are active in proportion to the active basis contained. In 
reality, these organic salts are generally quite unstable; their 
combinations are sometimes dissociated under minor influences, 
and it is, after all, the base alone that acts. 

The example of quinin has been taken advantage of for 
arguing that the same is true of the mercury salts and that 



204 PRINCIPLES OF THERAPEUTICS 

the efficacy of the latter depends solely on the quantity of 
mercury introduced into the organism at a given time. But 
how are we to determine this quantity? All that is known 
is the proportion of mercury contained in the various mer- 
cury salts, and no conclusion can be drawn therefrom, since 
it is agreed that the liberation of the metal and the time 
required therefor must also be taken into account. Now, we 
know too little regarding the conditions of dissociation and 
exchange of basis and of acid of mercury salts in the fluids 
of the economy to draw any conclusion whatever as to the 
relative efficacy of these salts, apart from the fact that an a 
'priori procedure is always a vicious method. It would be 
strange were this a priori realized in practice. And, as a 
matter of fact, clinics show such a difference of activity between 
the various salts of mercury (with equal doses of mercury) 
that it condemns the attempted establishment of analogy 
between the salts of quinin and those of mercury from the 
standpoint of importance of the quantity of active basis. 

So far the only conduct conformable to rigorous science 
is to consider the various salts of mercury in their combi- 
nations and to look for their relative clinical value, empiric- 
ally if so desired, according to the time and dose necessary 
to cure apparently similar lesions. The procedure is per- 
haps defective in so far as it is impossible positively to af- 
firm the absolute identity of two cases; but it is less so than 
a theory built on an hypothesis, and it is to clinical obser- 
vation that we must ultimately resort. Now, clinical facts 
demonstrate that the amount of mercury contained in the 
mercury salts is an element of insufficient and imperfect 
appreciation. 1 If we were to seek, outside of clinical ex- 
1 A. Manquat, Province medicale, December, 1906. 



VARIATIONS OF THERAPEUTIC ACTIVITY 205 

perience, elements of comparison between these salts, we 
should take into consideration, first of all, the organic or 
mineral nature of the acid (though there are notable differ- 
ences between the posology of the members of each group) 
and the degree of electrolytic dissociation. In spite of all, 
it would still be necessary to resort to clinical observation 
for confirmation of views derived from physico-chemical 
considerations. Is it not better to begin with clinical ob- 
servation and to do away with the habit of pretending to 
establish laws for therapeutics? 

In brief, a knowledge of the chemical constitution of a 
medicine is highly interesting from the view-point of possible 
creation of new medicines and from that of pharmacody- 
namic experimentation, but it is of far less importance to 
the practitioner. The latter views medicinal substances 
placed at his disposal as experimentation studies them and 
as clinical observation enables him to judge them. Herein 
properly lies his task. When anything that was not an- 
ticipated (dissociation, chemical instability, quantity of 
heat liberated in the combination, chemical saturation, tox- 
icity, local action, etc.) occurs, the clinician is obliged to 
reject a remedy which seemed to promise excellent effects. 
Such has been the case as regards so many homologues of 
cocain which have successively been tried according to theo- 
retical views and which have almost immediately been aban- 
doned. Reasons of a chemical order must have no influence 
on practice until sufficiently numerous accurate and con- 
vincing experimental researches have confirmed them, and 
the theoretical view has disappeared under the mass of facts 
implying a certainty. 



206 PRINCIPLES OF THERAPEUTICS 

The physiological and toxic actions of a substance are 
sometimes completely modified by their entrance into certain 
organic combinations. Thus arsenic, in the form of caco- 
dylate of soda, becomes latent or dissimulated and loses its 
high toxicity. Likewise mercury, in the form of hermo- 
phenyl or enesol, is tolerated in relatively very large doses. 

Added Action of Components. — There is still another 
remark to be made on the chemical composition of medi- 
cines: an attempt has sometimes been made to take advan- 
tage of the simultaneous action of the components of a sub- 
stance. Such has been the attempt to combine quinin with 
glycero-phosphoric acid or phytin, quinin with salicylic acid, 
guaiacol with cacodylic acid, etc. In order that a substance 
thus formed may prove efficacious it must fulfil a certain 
number of conditions. In the first place, the value of the 
components must not be contestable; in the next place, the 
components must enter into the medicine each with its active 
dose, and must preserve its activity; furthermore, the com- 
bination must be real and not a simple mixture; and, last 
but not least, the compound must be easy to employ. 

Some medicines of recent introduction may be judged 
by submitting them to the test of these conditions. Take, 
for instance, salicylate of quinin, proposed with a view of 
combining the actions of quinin and salicylic acid. The 
basic salicylate contains but 68.8 per cent, of quinin (that 
is, 5.2 per cent, less than does the sulphate) and 31.2 per 
cent, of salicylic acid. It requires no less than 900 parts 
of water to dissolve, that is, 150 parts more than does the 
sulphate. Thus, for the supposed advantage of combining 
salicylic acid and quinin, they have imagined a weak, very 



VARIATIONS OF THERAPEUTIC ACTIVITY 207 

difficultly soluble quinin salt and well-nigh useless as a sali- 
cylic compound, since no more than 0.312 grm. of salicylic 
acid combined with quinin can be given in twenty-four hours. 
Is it not preferable to prescribe the two medicines associated 
in the necessary doses? 

Many of these medicines dissociate as soon as they come 
in contact with water, so that, in reality, the two original 
substances are given in a mixture. This practice would 
have no inconvenience if the therapeutic results were satis- 
factory; but why speak of a body that does not exist, while 
it is so easy to remain within scientific precision by confining 
oneself to noting the advantages of associations to be com- 
posed at pleasure? 

INFLUENCE OF PHARMACEUTIC FORMS 

The first question, from the standpoint of pharmaceutic 
forms, is that of knowing whether it is preferable to prescribe 
the Galenic preparations of complex vegetable products or 
the definite, chemically pure principles that can be extracted 
from these products. Both these practices have had their 
convinced defenders. As is always the case in therapeutics, 
the truth is not in either of these systems; the definite prin- 
ciples have their indications as well as the Galenic prepara- 
tions. These indications are drawn from the end to be at- 
tained and from the facility of administration. 

Active Principles and Galenic Preparations. — Let us 
bear in mind that, according to Prof. Pouchet's investiga- 
tions, the albuminoid matters which accompany the active 
principles in plants, enable the economy to undergo, in a more 
intense manner, the action of crystalloids (glucosids, alkaloids) 



208 PRINCIPLES OF THERAPEUTICS 

with which they are associated. But we have already laid 
stress on the fact that this action on the organism needed to 
be measured and rendered accurate rather than intense. A 
potent activity is of no great importance, and it may even 
be undesirable, when a well-defined organic, functional, or, 
at times, symptomatic action is to be exerted. In this case 
it is obvious that active principles, being well-defined as they 
are (morphin, digitalin, spartein), have a marked superiority 
over Galenic preparations. But if the desired action is not 
well determined, as is the case with certain agents of nosocratic 
and of symptomatic therapeutics, we have no reason to prefer 
a definite principle, the action of which is sometimes doubtful, 
to the corresponding Galenic preparation of recognized utility. 
For this reason, it seems to me that colchicum is to be preferred 
to colchicin, the preparations carrying the totality of the prin- 
ciples of valerian to valerianic acid or its salts. Digitalis 
offers a fine example of this distinction: when we desire to 
exert an exclusively cardiac tonic action, as in asystole, we 
resort with success to the pure crystallized digitalin; but if 
we seek the special action of digitalis on pneumonia, an 
action that is not solely toni-cardiac, but carries some sort of 
semi-specificity, I believe the leaves of digitalis or, in their 
absence, its hydroalcoholic extract which best approaches it, 
should be preferred. 

In other instances the vegetable extract is to be prescribed, 
because the definite principle, on account of its great toxicity, 
is difficult to nandle; the extract of strophanthus, for ex- 
ample, is easier to manage than strophanthin, and the 
tincture of aconite than aconitin. 

Lastly, the facility of the mode of administration is also 



VARIATIONS OF THERAPEUTIC ACTIVITY 209 

to be considered: it is easier to take quinin than cinchona, 
pelletierin than the fresh bark of the pomegranate root. But 
as it is as easy to ingest semen contra as santonin, the for- 
mer which is more active than the latter is generally to be 
preferred. 

It is essential to offer the medicines in an efficacious, agree- 
able if possible, or at least acceptable form, and also in a form 
as little aggressive as practicable for the ways of introduction. 

Medicines are administered in liquid or solid form, more 
rarely in the form of vapor or gas, when it is to be diffused 
into the organism. 

When possible, the fluid form is preferable to the solid form. 
The fluid can have the degree of dilution most favorable to 
the tissues with which it is to come in contact; it generally 
facilitates rigorous dosage; it favors absorption; it avoids 
errors, as it is sometimes possible to judge the nature of a 
fluid by its appearance, density, color, taste, smell — characters 
which are often obscured when the solid form is employed in 
pills or wafers. On the other hand, the fluid form is imprac- 
ticable for certain substances difficult of solution or too dis- 
agreeable in taste. 

The solid form is in some cases necessary to ensure efficiency 
(subnitrate of bismuth, intestinal antiseptics, charcoal, etc.). 
In other cases it has the inconvenience of remaining inactive 
until after it is dissolved with more or less difficulty and irregu- 
larity in the digestive canal or in the tissues; it also necessi- 
tates a pharmaceutic preparation not always without disad- 
vantage (pills, wafers); lastly, it imposes upon the routes of 
introduction the maximum of local impression, generally 
more or less irritant and even painful. 
14 



210 PRINCIPLES OF THERAPEUTICS 

The fluid forms have a very variable density; this density 
sometimes renders the mode of administration somewhat 
peculiar (subcutaneous injection of thick oils; lipiodol, for 
example). 

Solutions. — The fluid form is in some cases the natural 
form of the substance (apiol, creasote, eucalyptol, castor oil, 
ether, etc.); in other instances the medicine has undergone 
solution in some appropriate fluid, such as water, alcohol, oil, 
wine, vinegar, beer, coffee, syrups, potions. Among the sol- 
vents, there are some which exert a special action not to be 
overlooked; for instance, wine, alcohol, coffee. 

The most rational solution is usually that of distilled steri- 
lized water, sufficiently diluted to obviate undesirable effects 
on the alimentary canal. Water does not alter the medicine 
and is generally well preserved. This form is limited by the 
insolubility or weak solubility of many substances in water 
and by the too bitter, nauseating, or disagreeable taste of 
certain drugs. The unpalatability may at times be corrected 
by addition of gum arabic or sugar (potions and syrups) or 
by a corrective (syrup of bitter orange peels, various essences) 
without any proper action of their own, or, more rarely, having 
a synergetic action. Solutions may be introduced into the 
organism in the form of enema (p. 159). 

Powders. — The simplest of solid forms is powder, but it 
is seldom so employed. An excellent form is the compressed 
(comprimes) , but few medicines are apt to take that form. 

The pill form demands very careful preparation, for dosage 
is very difficult, particularly when several medicines are 
associated in the same unit, because then there is danger of 
unequal distribution of the different substances to each unit. 



VARIATIONS OF THERAPEUTIC ACTIVITY 211 

This irregularity is especially to be feared when the respective 
doses of the components are widely different: centigrams 
associated with milligrams, for example (p. 125). The 
attempt has often been made to manufacture pills destined 
to traverse the stomach without being dissociated and dis- 
solved until after they have passed into the intestine. Two 
procedures are employed to this end, keratinization and 
glutino-resinous coating. 

Keratinization is due to Unna's inspiration. It consists in 
enveloping the pill in keratin, a substance extracted from 
corneous tissue which is not soluble until after it reaches 
the small intestine. It is quite a delicate operation; if imper- 
fectly managed, it does not prevent the pills from dissociating 
in the stomach. 

Glutino-resinous coating of Fumouze fulfils its purpose, 
but dissociation of the pill is extremely slow; it does not begin 
until four or five hours after ingestion and lasts at least four 
or five hours. Therefore, this procedure cannot be relied 
upon when rapid action is desired. Deliquescent (iodid of 
sodium) and explosive substances must not be prescribed 
in pills. 

In France pills are spherical. The flat, lenticular form 
of the English seems better, but is more difficult of prepa- 
ration. A pill weighs on an average 12 to 15 and at most 
30 eg. (from 2 to 5 gr.). 

Dragees are big pills (0.30 eg. to 1 grm.) coated with sugar. 

Granules are minute sugar-coated pills which weigh less 
than 5 eg. and contain, as a rule, from 1/10 mg. to 2 mg. of 
active principle. 

Wafers or cachets are a very convenient form of ad- 



212 PRINCIPLES OF THERAPEUTICS 

ministration of medicines. But they sometimes bring solid 
and irritant substances into contact with the stomach (quinin, 
salicylate of soda, etc.); besides, they imprison the medicinal 
substance and place them beyond all control. There has 
been conceived the excellent idea of shaping cachets in the 
form of small boxes which can be opened and closed at will. 
This is a far more convenient, cleaner, and safer form than 
the old. 

Gelules are small gelatin tubes to render the same ser- 
vice as the box- wafers, but they are more difficult to swallow. 

With globules, perls, capsules, capsulins, the medicine, gener- 
ally fluid (ether, creasote, copaiba, santal oil), is enclosed 
within a gelatin envelope, round for the first, ovoid for the 
two last-named. However, in practice, the designation is 
not strictly related to the form. The quantity of medicine 
contained in these envelopes varies from 5 to 50 eg. 

The form of pastilles, tablets, or pastes is suitable for 
medicines which are scarcely, if at all, alterable. Those prep- 
arations destined for action on the digestive tract are bene- 
fited sometimes enormously by the salivary secretion which 
they excite. Medicines are but seldom prescribed in the 
form of electuaries, opiates, conserves, biscuits, and chocolates. 

Suppositories, of frequent utilization, constitute a con- 
venient means to introduce into the rectum an active prin- 
ciple incorporated with a greasy body, which is, as a rule, 
cocoa butter. Gelatin and glycerin suppositories are also 
employed. Their weight is usually 3 to 4 grm.; they con- 
tain a maximum of 30 per cent, of active principle. 

Ovules enable us to introduce important topical reme- 
dies into the vaginal canal and favorably modify the cervix 



VARIATIONS OF THERAPEUTIC ACTIVITY 213 

uteri. The active remedy is incorporated with a mixture 
of glycerin and gelatin. 

Crayons are of two kinds: some contain the pure medicine 
(silver nitrate); others, designed to carry a modifier into 
narrow channels (cervix of uterus, fistulae), contain the remedy 
incorporated with a solid body (gum arabic, cocoa butter, 
gelatin). 

Specialties. — Special mention is due to pharmaceutic 
specialties on account of the importance they have assumed 
of late years. In order to judge the value of specialties it 
is necessary to distinguish those which represent a medicinal 
substance in its state of purity (simple specialties) from those 
which represent an association of medicines (compound special- 
ties) . The former offer great advantages when they are manu- 
factured by the firm which prepares the original substance 
in as perfect a state of purity as possible or when it offers a 
reliable guarantee against all adulteration; the latter necessi- 
tate the greatest reservations. In fact, it is very useful, in 
certain cases, to be able to prescribe a product of prime im- 
portance, such as quinin, digitalin, spartein, theobromin, etc., 
with the assurance that it will have all its activity and all its 
purity of activity. Upon the excellence of these medicines 
may depend a patient's life. In such cases it is indispensable 
to prescribe a specialty of recognized excellence. It is also 
hardly necessary to say that this quality demanded of a spe- 
cialty does not belong exclusively to that particular form of 
preparation: many pharmacists can offer the same medicines, 
as good as the best specialties and with the same guarantees. 

It is well to bear in mind that among the manufacturers of 
specialties, even simple and excellent ones, there are many 



214 PRINCIPLES OF THERAPEUTICS 

who do not themselves prepare the products which they deal 
in: they secure them for themselves from the same sources 
as do pharmacists and do nothing more than give them an 
appropriate pharmaceutic form. 

The aim in view is the quality of the medicine; a specialty 
is but one of the means to carry out the aim and to obviate 
the chances of having the most indispensable medicines either 
inactive or dangerous on account of impurities or modifications 
in their mode of preparation. Certain products are particu- 
larly subject to great variations of action according to their 
origin, such are theobromin, quinin, salicylate of soda, 
digitalin, aconitin, atropin, chloroform, and the iodids. 

Not all specialties, even the simple and carefully prepared 
ones, can be recommended. Such are those which represent 
the pharmaceutic realization of an unfortunate idea, gener- 
ally supported by insufficient facts or the mere product of 
some fanciful theory. 

The compound specialties which crowd the drug-stores are 
far less defendable. Excepting a very small number among 
them that are excellent, they are, as a rule, associations the 
principle of which, purely theoretical, has been conceived by 
a more or less ingenious pharmacist aided or not by a physi- 
cian. Thus are inflicted on the innocent public cough syrups, 
containing codein, morphin, aconite, sometimes polygala, bro- 
moform, pectoral infusions; analgesic wafers and comprimes; 
purgative pills; some hypnotics. In some instances creasote 
is associated with some supposedly restorative element or 
with some sedative to make a specific for tuberculosis. 

These products are innumerable. Their rational utiliza- 
tion is restricted by the contraindications which one of the 



VARIATIONS OF THERAPEUTIC ACTIVITY 215 

active components of the mixture may impose in a given 
case — that is, by the fear of a special intolerance of the 
patient to this component; for instance, aconite, which is 
often associated with codein, finds numerous contraindica- 
tions. The same is true of cocain, of bromoform. Nor are 
grave accidents occasioned by specialties altogether unre- 
corded. It would be a fortunate occurrence, indeed, if the 
composition and preconceived proportions of the components 
should happen to be just suited to a given case. Therapeutics 
demands more accuracy. 

There is another important remark to make concerning 
the great majority of simple or compound specialties, and 
even the best among them: the prospectus and directions ac- 
companying the medicaments are not to be depended upon either 
for indications or for doses. The indications are almost always 
extended beyond measure and the doses are too large. 

What is to be said of those specialties the exact composition 
of which is not known? As a matter of principle, they are to 
be condemned and must not be prescribed, but only as a 
matter of principle, because true science does not reject any- 
thing without a previous examination: Nihil contemnendum. 
Simply they must not be prescribed without satisfactory 
reasons which are almost always, in such a case, the opinion 
of a truly conscientious observer qualified for such observation. 

Physicians do not take enough interest in pharmacy which 
is such a powerful factor in medicinal therapeutics and its 
development. The spread of specialties may exert a very 
great influence on this development and render the future 
existence of pharmacy doubtful, since, if physicians fall into 
the easy habit of prescribing nothing but specialties, pharma- 



216 PRINCIPLES OF THERAPEUTICS 

cies will soon become mere storehouses of specialties. It is 
to the interest of the physician that pharmacies should pros- 
per, and he must therefore oppose the invasion of specialties, 
but on condition, of course, that the pharmacies be strictly 
correct. If this correction should seem impossible, then the 
monopolization of pharmacies by the State should be thought 
of. Such monopolization would produce certain immediate 
results: suppression of illegal practice of medicine by phar- 
macists, good pharmacy in the hands of scientific men, as is 
the case in the pharmacies of great hospitals; lastly, from 
the therapeutic standpoint, certainty of prescribing only ade- 
quate and always identical products. 

Asepsis of Preparations. — The justification of this view 
results from the necessities which modern therapeutics imposes 
upon pharmacy. The time has gone when mineral salts, 
plants, and rare alkaloids can satisfy all the requirements of 
the medical art. The number of delicate and highly toxic 
chemical products is now legion; it is no longer reasonable 
to put them into the hands of any student who is a stranger 
to the responsible pharmacist. On the other hand, asepsis, 
which has assumed so important a place in therapeutics, does 
not yet reign in all pharmacies. Aqua simplex, or rain water, 
and a disregard of a hundred little requirements of strict 
antisepsis still constitute the pitfall of many pharmacies. 

Asepsis is as indispensable to pharmaceutical preparations 
as to medical and surgical practice. All pharmaceutic prod- 
ucts (and I do not mean alone solutions destined for cuta- 
neous injections) should be sterile. Without this precaution, 
syrups, potions, and solutions alter, salves and sparadraps 
may infect wounds; contaminated water may engender dis- 



VARIATIONS OF THERAPEUTIC ACTIVITY 217 

ease; in brief, owing to deficient antiseptic precautions, the 
expected results from the employment of medicines are not 
obtained and sometimes unexpected accidents occur (erysip- 
elas, erythemata, furuncles, intestinal infections). I have 
more than once emphasized the necessity of medical education; 
that of pharmaceutic education is as great. 

INFLUENCE OF THE ROUTE OF INTRODUCTION OF MEDI- 
CINES INTO THE ORGANISM ON THEIR ACTIVITY. 

For a long time hardly any other route than the alimentary 
canal was known for the administration of medicines. This 
is still the simplest and most commonly employed pro- 
cedure, but not always the best to be recommended. Sub- 
stances introduced into the stomach often lose some of their 
activity for several reasons: first, because absorption is slow 
in the digestive tract, particularly in the stomach; it is espe- 
cially so if, the pylorus giving irregularly passage to the stom- 
ach contents, medicines slowly arrive in the intestine which 
is the usual seat of absorption. Again, the contents of the 
digestive tract alter a certain number of medicines (caco- 
dylate of soda, for instance). On the other hand, certain 
substances do not become active except after solution in the 
stomach, and if this operation is rendered incomplete through 
insufficiency of the gastric juice, the remedy remains in- 
active (sul phonal). The liver also intervenes to retain and 
fix partially certain substances (mercury), and to lessen the 
activity of certain others. The posology of preparations 
introduced into the digestive canal is therefore somewhat 
special and higher than when the mode of entrance is more 
direct. Lastly, the contact of remedies with the digestive 



218 PRINCIPLES OF THERAPEUTICS 

mucous membrane is not always harmless. In conclusion, 
if the digestive tract remains and will always remain the 
route most commonly employed for the introduction of medi- 
cines into the economy, it can be so only under certain con- 
ditions of tolerance, functional regularity, and indifference 
as to the rapidity of intervention. 

Subcutaneous, Intramuscular, and Intravenous Injec- 
tions. — Under other circumstances, that is, when we desire to 
spare the digestive organs and to exert a sure, rigorously dosed, 
and speedy action, we resort to other modes of introduction, 
the most usual of which consists in hypodermatic injections. 
These injections have become more common since their em- 
ployment has been rendered inoffensive, thanks to the prac- 
tice of rigorous asepsis in their management. The syringe 
also has undergone improvements. One of glass or crystal, 
with a piston of the same substance, is now mostly employed. 
In fact, all models are acceptable on condition that they 
be used only after sterilization. 

The capacity of these syringes varies from 1 to 20 c.c; 
we are far from the primitive Pravaz syringe, of invariably 
1 c.c; the most practical model is probably that of 3 c.c, 
with which injections of 1 to 5 c.c can readily be practised. 
However, the one of 1 c.c, corresponding to the mos': fre- 
quent dosage, has the advantage of obviating a cause of error. 
For serums the 10 c.c size is most suitable. 

The iridiated platinum needles, which endure red-hot tem- 
perature without alteration, are the precious and indispen- 
sable complement of the glass syringe. The solder must be 
in silver in order to resist all temperatures of flame. 

The only obstacles to the still more frequent use of hypoder- 



VARIATIONS OF THERAPEUTIC ACTIVITY 219 

matic injections are: the irritant or painful properties of cer- 
tain medicines for the subcutaneous tissue, the volume of 
the medicine, its solid or hardly soluble state outside of the 
digestive canal (hypnotics in general), and the suspicion of 
superfluous calls by the physician. 

The first of these obstacles is sometimes removed by the 
employment of intramuscular injections, which are far better 
tolerated but which necessitate precautions and offer dif- 
ficulties already referred to (p. 158). 

Another means of rendering subcutaneous injections toler- 
able is to dilute the solutions far more than is usually done. 
Neutral hydrochlorate of quinin is a fine illustration. A 
dose of 0.50 eg. of this salt is put in 1 c.c, a fearful concen- 
tration resulting from the antiquated habit of formulating 
solutions for subcutaneous injections in view of one volume 
of the primitive Pravaz capacity. Of course, with such a 
solution pain and, often, abscesses are produced. How 
could it be otherwise? In order to put 1/2 grm. of the salt 
in 1 c.c, it is necessary to make the solution in 0.60 of water. 
When such a solution enters the tissues, there results, owing 
to dissociation, about 0.05 eg. of pure hydrochloric acid. 
It is just as if one had injected under the skin a 5 per cent, 
solution of pure hydrochloric acid in addition to the quinin! 
But if we inject a solution containing only 0.15 of the neu- 
tral hydrochlorate of quinin to the cubic centimeter, we 
can then inject 0.45 of the salt in 3 c.c, and the quantity of 
free hydrochloric acid will be sufficiently diluted not to exert 
any caustic action. In the case of a very delicate subject 
(child, adolescent, woman), the solution may very well be 
further diluted so as to have . 50 of quinin salt in 4 or 5 or even 



220 PRINCIPLES OF THERAPEUTICS 

more cubic centimeters. And there is no more difficulty in 
injecting this volume of fluid than the usual quantity of 1 c.c. 

On the other hand, pharmacists and chemists are endeav- 
oring to find substances inoffensive for the tissues. To 
this effect, formiate of quinin has been proposed by Dr. La- 
croix as a substitute for the hydrochlorate. Electrargol, 
substituted for collargol, has made it possible to inject under 
the skin colloidal silver. 

The farther from the dermis subcutaneous injections are 
practised, the b tte:- they are borne. The needle must there- 
fore penetrate into the deepest part of a large fold made in 
the skin. If the cellular tissue is abundant, as in the buttock, 
it is simpler to drive the needle perpendicularly to the cuta- 
neous plan, and to its full length, through the skin squeezed 
between two fingers of the left hand. 

The regions richest in loose cellular tissue are the most 
favorable for injections (buttocks, interscapular region, 
flanks, abdomen). The regions traversed by numerous veins 
are to be avoided. Under certain circumstances, it is ad- 
visable first to withdraw the needle to see whether any blood 
runs from it before making the injection, in order to be cer- 
tain not to inject the solution into a vein. 

It is said that the hypodermatic method opens the door to 
abuse of intervention on the part of the physician. This 
reproach may sometimes have a foundation, but a conscien- 
tious physician will never be suspected of abuse. He will 
have the tact of proposing injections, to be made by himself, 
to those alone who can afford it. For others, he will make 
various arrangements. At times he may make one free of 
charge; at others he will appeal to a nurse or to some member 



VARIATIONS OF THERAPEUTIC ACTIVITY 221 

of the sufferer's family to whom he will demonstrate the 
way to make a subcutaneous injection. In so doing, he will 
use his best judgment not to give occasion to worse abuses 
by intrusting to ignorant hands a practice which is so open 
to all sorts of abuse and danger. To practise aseptically 
a hypodermatic injection is not so simple as it may seem when 
medical education is lacking. 

In cases of urgency, when it is indispensable at once to 
obtain a rapid and energetic action, one may resort to intra- 
venous injections which exert the maximum of medicinal 
activity. But this route is very limited and its utilization 
exceptional; it supposes, in fact, that the injected fluid will 
be perfectly miscible with the blood, that it will not notably 
alter its elements, that its action will not be too abrupt, that 
the operator will be somewhat of a surgeon, and that, lastly, 
the injection will not be the point of origin of a coagulation 
of fibrin. 

Enemata. — The rectal route comes to the assistance of the 
foregoing procedures when the latter are contraindicated. 
It is probably not utilized enough. Provided the anus is 
healthy, the rectum may often enable one to avoid the hypo- 
dermatic route. However, it is necessary to spare the rectum 
whose susceptibility to certain medicines is very keen (to 
mercury for instance), and to repetition of contacts. Exceed- 
ingly painful rectitis may readily be produced. Repeated 
alimentary enemata are to be avoided as much as those of 
irritant substances. It is also known that the rectum does 
not easily absorb acid solutions. For this reason the adminis- 
tration of quinin by means of enemata is a defective procedure. 
On the other hand, creasote, incorporated with a greasy body, 



222 PRINCIPLES OF THERAPEUTICS 



» 



iodids, belladonna, morphin, etc., are very well tolerated 
and absorbed by the rectum. This procedure is not suitable 
for medicines that must slowly enter the circulation (p. 159.) 
Therapeutic enemata are best tolerated if the rectum is first 
washed with a simple enema and if the fluid to be retained 
is tepid and injected high into the intestine. 

Absorption by the Skin. — Penetration of medicines through 
the skin (epidermic method) may be the subject of considera- 
tion from the viewpoint of experimentation and of practice. 
The latter alone will occupy us. The skin covered with the 
intact epidermis absorbs too little to serve therapeutic pur- 
poses except in the case of gases and volatile substances; but 
if the epidermis is altered either by prolonged friction or by 
irritant substances, it can absorb remedies dissolved or incor- 
porated with greasy substances. Hence these practical con- 
clusions: 1. not to count on the absorption of any but gases 
and volatile substances; 2. to favor absorption of substances 
by means of previous cleansing and vigorous and prolonged 
friction; 3. never to leave very active substances in contact 
with the skin, especially in children and persons with a 
tender skin, believing that there is no danger of absorption, 
since, if the epidermis has suffered any alteration, 1 unexpected 
absorption may result. 

The skin therefore constitutes a restricted and irregular 
way of introduction, but a very precious one whenever avail- 
able, because of its continuous absorption and usual freedom 
from inconvenience. It is especially utilized for mercury, 

1 Substances that might penetrate into the excretory ducts of the seba- 
ceous and sudoriparous glands would probably be absorbed by the capillary 
network surrounding these glands, as Furbringer has demonstrated it in 
regard to mercury. 



VARIATIONS OF THERAPEUTIC ACTIVITY 223 

salicylate of methyl and the like, certain iodic compounds and 
collargol; but the skin also absorbs iodin guaiacol, chloroform, 
ether, and perhaps chlorid of sodium (Garrigou), atropin, 
and pilocarpin (Aubert). 

Intratracheal, Spinal, and Intraviscual Injection. — 
The other routes of introduction (intratracheal, spinal, intra- 
visceral) are but exceptionally employed on account of the 
drawbacks and sometimes dangers. As to spinal anesthesia, 
it seems to offer more inconvenience than advantage and 
must have a very restricted utilization. 

Absorption by Wounds and the Mucous Membrane. — 
The toxic phenomena caused by the accidental absorption of 
tonic substances through wounds (iodoform, phenol, bichlorid) 
or through mucous membranes (cocain, mercury) render it 
necessary not to leave large doses of active medicines too 
long in contact with absorbing surfaces. 

VARIATIONS OF ACTIVITY ACCORDING TO THE DIS- 
TRIBUTION OF THE DOSE. 

Massive Doses. — The proper distribution of the dose is 
one of the most important points to consider in the adminis- 
tration of medicines. An active dose may prove too strong 
and dangerous if taken at once, whereas, if divided and 
distributed through the twenty-four hours, it may produce 
the best results. Thus, salicylate of soda and its derivatives 
produce their full effect in acute articular rheumatism only 
in a large dose; but if this dose is taken at once, it produces 
toxic effects; if the necessary amount is given in fractional 
doses during the twenty-four hours, it proves rapidly curative. 
On the other hand, an amount which would be active if taken 



224 PRINCIPLES OF THERAPEUTICS 

at once ceases sometimes to be so as a result of division into 
too many fractional doses. Such is the case with quinin 
in malaria: a dose of 0.80 to 1 grm. of the sulphate, taken 
in two or three fractional doses eight to ten hours before the 
presumed occurrence of the paroxysm, almost certainly pre- 
vents the recurrence of a paroxysm of average intensity. The 
result would have been far less certain if the same quantity 
was given in fractional doses through the twenty-four hours. 
Hypnotics and purgatives also, to be effective, must be 
given in a somewhat massive dose. 

Fractional Doses. — The division of the amount into frac- 
tional doses insures the continuity of medicinal action. It 
is of such importance that it may completely transform this 
action; thus calomel, in a massive dose, is simply purgative; 
in fractional doses it makes a notable quantity of mercury 
penetrate into the economy. 

We have* already spoken (p. 126) of fractional doses with 
reference to tolerance and of alternation of medicines (p. 109) 
in order to obviate inactivity by habituation and intolerance 
by accumulation. 



CHAPTER X 
NON-MEDICINAL THERAPEUTIC ACTIONS 

(Physiotherapy) 

Physiotherapy — Hygienic actions — Psychic actions — Mechanical actions 
— Physical actions — Surgical actions. 

If it was restricted to the administration of medicines, 
therapeutics would very often be impotent and disappointing. 
In certain cases medicinal action enjoys a preponderance which 
it owes to its intensity of action and its immediate results that 
consist sometimes in a cure, sometimes in marvelous soothing, 
sometimes in functional restoration of an essential organ, 
such as the heart — restoration capable of preventing immi- 
nent death; but in a very great multitude of other circum- 
stances the physician cannot get along without the thera- 
peutic actions of a different order, which always accompany, 
more or less, medicinal action and which sometimes become 
even preponderant. It would therefore be a grave error to 
limit therapeutics to the utilization of the means furnished by 
materia medica and chemistry. 

Non-medicinal therapeutics most frequently utilizes the 
favorable modifications that may result from the effect of 
natural agents and the influence of environment. The latter 
offer the inappreciable advantage of being utilizable for a very 
long period of time without giving rise to either intolerance 
or injurious habituation (climate, diet, exercise, rest); they 
*5 225 



226 PRINCIPLES OF THERAPEUTICS 

may sometimes be employed during an entire lifetime (climate, 
diet). 

The name physiotherapy (Landouzy) has commonly been 
adopted to designate the group of therapeutic actions derived 
from the employment of natural agencies, such as water, air, 
climate, electricity, etc. Physiotherapy includes all the medi- 
cations which borrow their agent from natural materia medica. 
Physiotherapy has thus taken in the greatest part of non- 
medicinal therapeutic actions, and even hydro-mineral medi- 
cation. This chapter might even be given the title physio- 
therapy, if it had not been necessary to make space, within 
non-medicinal therapeutics, for surgical therapeutics and 
prophylactic hygiene. 

Physiotherapy includes to-day: hydro-mineral medication, 
hydrotherapy, climatotherapy, electrotherapy, phototherapy, 
orthopedia, kinesitherapy, mechanotherapy, dietetics. 

We shall 'divide non-medicinal therapeutic actions into five 
groups: hygienic actions, psychic actions, mechanic actions, 
physical actions, and surgical actions. 

HYGIENIC ACTIONS AND THERAPEUTIC HYGIENE 

Perhaps more than any other science, therapeutics needs 
accuracy on account of its great complexity that is liable to 
lead to confusion of ideas. Hence it is that hygiene, according 
to its etymology (vytW, health) is defined "the part of med- 
icine which dictates precepts for preserving health and 
preventing the development of disease" (Roger). If this is 
so, there would never be any occasion for calling into play 
the ideas of hygiene in therapeutics, since the latter is applied 
only to the state of disease. At all events, this idea has been 



NON-MEDICINAL THERAPEUTIC ACTIONS 227 

advocated by therapeutists of no mean standing. But it 
will suffice to open a treatise on hygiene to be convinced 
that the definition of hygiene quoted above is obviously 
incomplete: it is applicable to prophylactic hygiene alone. 

In reality hygienists have extended the horizon of their 
thoughts far beyond prophylaxis: they have endeavored to 
appreciate accurately the influence on health of all media, 
of ingesta, and of voluntary activity. Hygiene may there- 
fore be defined: the department of medicine which studies 
the influence of environment, of ingesta, and of voluntary activi- 
ties on the organism in a state of health. 

It is then an easy matter to define therapeutic hygiene as the 
study of the influence of environment, ingesta, and voluntary 
activities on the diseased organism. Therapeutic hygiene thus 
promotes the optimum of activity of the organism weakened 
by disease and favors recovery or prolongation of life. It is 
neither physiology, which studies only the play of func- 
tions, nor hygiene, which confines itself to the study of modi- 
fications impressed on these functions by various influences 
affecting the healthy man in his relations to the external 
world; but it is an integral part of therapeutics, and becomes 
independent of all other sciences in taking up on its own 
account the same subjects of study as does hygiene, but 
applied to the sick. 

Prophylaxis exactly belongs to hygiene, but there is also 
a prophylactic therapeutics, which intervenes to prevent the 
development of a disease whose germ has just been inoculated 
or may have been inoculated (antitetanic serum, antidiph- 
theric serum). The means of this therapeutics are not there- 
fore included in the proper sphere of hygiene. 



228 PRINCIPLES OF THERAPEUTICS 

The conception of therapeutic hygiene as set forth above 

permits enumeration of its means very plainly and completely : 

I, Influence and utilization of environment in 

FAVOR OF THE SICK. 

1. Abstract elements of natural environment: Soil; water; 
air; external temperature; atmospheric pressure. 

2. Associated natural elements: Climate; mineral waters; 
thermal waters. 

3. Environmental elements derived from industry and human 
activity: habitation; clothing; cleanliness. 

4. Social environment and groupings: City; country; pro- 
fession; social position; army; school; prisons. 

II. Ingesta. 

Alimentation of the sick: Dietetics. 

III. Voluntary activities. 

1. Exercise, gymnastics: Kinesi therapy. 

2. Rest: Physical; intellectual; sexual. 

Among these influences there is none that cannot be util- 
ized in therapeutics: some of them belong to functional thera- 
peutics (climate and its elements, hydrotherapy, exercise, 
rest, human environments); others are concerned in repara- 
tive therapeutics (dietetics). Some are applicable to all 
patients as to all human beings, but are more urgent and 
more delicate of utilization in the former: such are condi- 
tions of habitation, heating, ventilation, clothing, and per- 
sonal cleanliness, etc.; others have been elevated to the dig- 
nity of true therapeutic procedures, sometimes almost ex- 
clusively so. In fact, while most of these means secure no 
more than a modus vivendi, placing the sick under the best 
possible conditions of recovery or survival, there are among 



NON-MEDICINAL THERAPEUTIC ACTIONS 229 

them some that possess true curative action. Dietetics, 
for instance, constitutes an essential part of infantile thera- 
peutics: water diet in acute gastro-enteritis of the first year 
or two, is a truly curative factor. How many disorders of 
this tender age (vomiting, diarrhea, insomnia, eczema) yield 
to simple regulation of doses of milk. Later on, digestive 
disturbances find no remedy but in appropriate diet the ele- 
ments of which have in recent years been enriched (babeurre 
fermented milks, Armenian matzoon or Zoolak, maltins, 

etc.). 

In the case of adults diet (with or without mineral waters) 
has become the basis of treatment of gastro-intestinal af- 
fections, particularly of ulcer of the stomach with or with- 
out hemetemesis, of dyspepsias, of muco-membranous en- 
teritis, of nutritional diseases (diet of diabetic, gouty, and 
oxaluric subjects), of uricemia (diet devoid of purine bases), 
of epithelial nephritis (diet in albuminuria). In acute dis- 
eases the importance of dietetics is just as great. 

In many cases it is possible to form a good therapeutic 
scheme without medicines; but in very few instances is it 
possible to arrange one without dietetics. How often a 
medicine usurps the credit due to concomitant hygienic in- 
fluences in successful treatments! 

It is right to separate water from the elements of dietetics 
on account of its major importance. Water, perhaps, is not 
a medicine properly so called, but it is the first and the most 
indispensable of remedies. Apart from the role it plays in 
the phenomena of life, water has the advantage of infiltrat- 
ing everywhere, diluting all the soluble waste materials of 
the organism, favoring all secretions and all excretions, pro- 



230 PRINCIPLES OF THERAPEUTICS 

moting particularly diuresis, perspiration, and bilary excre- 
tion. It is the main depurator of the organism. The thera- 
peutic action of Evian water, which is almost entirely free 
from all minerals, is an evidence. There are in France a great 
number of sources presenting the same purity and absence 
of mineralization as Evian; it is to be regretted that they 
are not utilized, as they might be, for chronic cases which 
need this lixiviation which water alone can accomplish tuto, 
cito, and jucunde. 

In view of the modifications which they produce in the 
organism, appropriate changes of climate are utilized to ame- 
liorate various morbid states such as malaria, rheumatism, 
asthma, pulmonary emphysema, chronic catarrhal conditions, 
certain nervous manifestations (insomnia), neurasthenic states, 
in a large measure dyspepsia and constipation, anemia, scrof- 
ulosis, certain forms of pulmonary tuberculosis. The ma- 
rine cure favors recovery from certain scrofulous manifes- 
tations (adenophathias). 

In other instances climate acts as a therapeutic adjunct. 
But I must again dwell, as I have done in other publications, 1 
on its power to increase the longevity of valetudinarians and 
of the aged. In fact, in certain climates there are found con- 
ditions of temperature, pressure, dryness, or humidity of the 
air, of calm, etc., by means of which the function of important 
organs attains its maximum of perfection. If those condi- 
tions which best meet the requirements of the organism are 
successfully found, the organs that suffer without being too 
deeply affected are placed in an optimum of functional activ- 

1 Bulletin medical, November 27, 1901; January, 1902, and report to the 
Congres de climatotherapie et d'hygiene urbaine of Nice, 1904. 



NON-MEDICINAL THERAPEUTIC ACTIONS 231 

ity which constitutes for the patient a new life, and if it does 
not practically amount to recovery, it realizes at least a per- 
manent amelioration ensuring prolongation of life. Thus 
cardiac subjects will experience from a long sojourn in a very 
warm country a premature fatigue of the heart, which may 
be avoided in a climate with a moderate temperature and 
calm air; those suffering from catarrh will benefit by spending 
the winter in a a warm country, etc. 

I have shown in a previous work 1 that the optimum of func- 
tional activity of an organism may be realized in three differ- 
ent ways by change of climate: 1. By a compensating adapt- 
ation resulting from an effort of the cells and the organs to 
enable the organism to live in the new climate. From this 
functional effort there results, without intervention of medi- 
cines, a new activity of the organism, more favorable than the 
accustomed one, if the climate responds to the indications 
furnished by the patient's state. These compensations are 
especially remarkable in altitudes, in cold and in hot countries. 
2. By stimulation, that is, by the excitation exerted by certain 
climatic elements on depressed functions. This process differs 
from the preceding one in that the stimulation, in view of the 
adaptation of the organism to environmental conditions, 
is a necessity from which there is no possible escape, because 
it is a vital condition, while stimulation by climatic elements 
may be unattended by any marked effects, owing to a lack 
of reaction on the part of the organism. 3. By the choice of a 
passive environment in the midst of which the organism will 
have to make no useless effort of adaptation and will be ex- 

1 A. Manquat, " I/adaptation en climatotherapie." First French Con- 
gress of Climatotherapy, Nice, 1904. 



232 PRINCIPLES OF THERAPEUTICS 

posed to no harmful excitation. Therein, no organ and no 
function will undergo the slightest fatigue: the injured organs 
and the weakened organisms will recover their optimum of 
activity without being exposed to any disturbing influence. 
Aged, cardiac, and nephritic patients, certain neuropathic 
subjects, the tuberculous (active forms), syphilitic, and 
those suffering from catarrh and eczema, can be particularly 
benefited by a passive environment. 

It is possible also to isolate, as it were, the climatic elements 
and to benefit by the favorable ones, while guarding against 
those that might prove harmful. This can readily be . ccom- 
plished by means of contrivances of habitation and clothing 
and mode of life. These artificial conditions extend consider- 
ably the range of action of climate. It is with climates as 
with all therapeutic agents: they have their indications, their 
posology, and their mode of administration. 

Mineral waters might be considered as medicines if their 
physico-chemical complexity so easily dissociable (composi- 
tion, radio-activity, thermality, gasification) and their place 
in the natural materia medica did not assign them a privileged 
rank in physio-therapy, and did not distinguish them from 
medicines properly so-called. They are powerful therapeutic 
means, capable, according to their nature, of correcting digest- 
ive troubles, constipation, and abdominal circulation, of 
calming the nervous system, of washing all the emunctories, 
of equilibrating deficient nutrition, of effectively acting on 
altered mucous membranes, dermopathies, visceral and arti- 
cular congestions, etc. Traveling facilities and the modern 
strenuous life assure to these therapeutic measures an ever- 
growing development. 



NON-MEDICINAL THERAPEUTIC ACTIONS 233 

Hydrotherapy is a method of choice for equilibration of 
nervous dynamism and modifying local circulations. 

Cold bathing in typhoid fever and, under certain circum- 
stances, in the course of other infectious diseases, is a heroic 
means to favor or re-establish diuresis, support the failing 
nervous system, stimulate circulation, and combat hyper- 
pyrexia. 

Country life for the tuberculous, city life for rheumatic suf- 
ferers and for those predisposed to hay fever are therapeutic 
adjuncts of the first importance. 

Rest, or even rest in bed, in neurasthenic states, chlorosis 
and tuberculosis, becomes sometimes a curative procedure. 
Complete rest retards the evolution of general paralysis. In 
nervous syphilitics, intellectual and sexual rest are considered 
as prophylactics, the former against general paralysis, the 
latter against tabes. 

Furthermore, hygiene is of preponderant value for all sub- 
jects afflicted with some definitive lesion, such as cardiopathy 
chronic nephritis, certain liver ailments. It permits adjust- 
ment of the mode of life of patients to their forces, alimenta- 
tion to their digestive capacity, and their power of depura- 
tion. Whoever, suffering from a decline in the resistance of 
an essential organ, knows how to harmonize his expenditure 
with his real dynamism, finds himself in fact, and at least for 
long years, in the condition of a well man (mitral stenosis 
for instance). All such subjects are in the same situation as 
a horse suffering from intermittent claudication who does 
not limp except when he exceeds his measure of speed. 



234 PRINCIPLES OF THERAPEUTICS 



PSYCHIC ACTIONS 

Psychic actions are those that act on the patient's mind. 

The psychic treatments constitute psychotherapy. This 
includes: suggestion, reasoning, education, re-education of vari- 
ous psychic faculties; it is aided in certain cases by environ- 
mental influences, especially isolation, and by some somatic 
treatment. 

I exclude charlatanic suggestion and that conveyed by 
the employment of medicines or physical agents, not that 
they are incapable of overcoming certain morbid manifes- 
tations, but because they are unworthy of scientific thera- 
peutics. I repeat that the first duty of the therapeutist, 
who wishes to be absolutely honest, is to be conscientious. 
Whoever systematically deceives his patients, even though 
for a praiseworthy object, lacks this qualification. I have 
read opinions to the contrary, upheld by most serious men. 
I can by no means approve of them. I do not deny that, 
in certain exceptional cases, deception may be legitimate, 
as, for instance, when a patient's mentality is too enfeebled 
to admit the influence of reasoning. In the case of a mor- 
phinomaniac who did not de ire to be cured, it would cer- 
tainly be permissible to diminish the dose of morphin with- 
out letting him know; but such a procedure seldom succeeds. 

Cures secured by deceiving the patient are far from reli- 
able. If the physician gives a medicine or pretends to per- 
form an operation for removal of an imaginary foreign body, 
and the cure seems to be radical when the patient is shown 
a needle (or a serpent, as the case may be) seemingly ex- 



NON-MEDICINAL THERAPEUTIC ACTIONS 235 

tracted from his body, the trouble may soon reappear if the 
sensation which gave rise to the false idea persists. 

In a weak-minded subject suffering from an acute state, 
the physician is evidently authorized to administer a medi- 
cine which the patient fears but which is strongly indicated, 
such as digitalis, salicylate of soda, colchicum, or, on the 
contrary, withhold the use of certain medicines in which the 
sufferer has great faith, without, in either case, letting him 
know. But such procedures, leading the patient to believe 
that he is taking a certain medicine when he is taking a dif- 
ferent one, are repugnant to the physician who will not re- 
sort to it except in exceedingly rare cases. They do not 
deserve to enter the sphere of scientific therapeutics. Even 
those that might act on the patient's mind do not belong to 
psychotherapy properly so called. 

There remain, therefore, as psychotherapic procedures, 
suggestion, reasoning, and education of psychic faculties. 
The latter may be aided by isolation and certain moral cir- 
cumstances, such as religious faith, the affectionate and moral 
character of the entourage, by confidence and, last but not 
least, by the physician's authority. 

The value and range of influence of suggestion has recently 
been much discussed. As in most controversies, the defini- 
tion of the word has perhaps been too much overlooked. 
What is suggestion? Since the time of Braid, the majority 
of authors define suggestion as a procedure by which there 
are developed in the mind of a patient certain ideas which 
would not exist spontaneously. But Braid had in view par- 
ticularly hypnotic suggestion. Dr. Bernheim, one of the 
authorities who best know what suggestion is, has extended 



236 PRINCIPLES OF THERAPEUTICS 

beyond measure the meaning of this word; he defines sug- 
gestion: the act by which an idea is introduced into the brain 
and accepted by it. Every idea accepted by the brain would 
thus constitute a suggestion for Dr. Bernheim. Taken in 
this sense, suggestion would include the whole of psycho- 
therapy, since persuasion, reasoning, and education develop 
and introduce into a patient's brain new ideas as well as, 
or better than, does pure and simple affirmation. No dif- 
ference is more evident, however, among therapeutic pro- 
cedures than that of suggestion from reasoning. I think 
Babinski was one of the first to seek to establish a distinc- 
tion between suggestion and persuasion. For this author 
the word suggestion must express "the act by which we en- 
deavor to make another accept, or make him realize an idea 
obviously unreasonable/' * and the word persuasion must 
be applied to ideas that are reasonable or at least not op- 
posed to common sense. 

Is this distinction legitimate? In the first place it can be 
criticized because it suppresses the suggestion of therapeutics. 
For, if suggestion serves only to cause acceptance of unreason- 
able ideas it is hard to see for what it can ever be good. The 
trouble would not be great if it was shown that, in all cases, 
persuasion could replace suggestion; but a profound and accu- 
rate study of a great number of cases of cures by simple per- 
suasion would be necessary to demonstrate the uselessness of 
suggestion. Moreover, if suggestion is a procedure causing an 
idea to be accepted, what does it matter whether this idea 
is or is not reasonable? The procedure, nevertheless, persists 

1 J. Babinski, " Ma conception de l'hysterie et de l'hypnotisme." Bull, 
de la Soc. de Vinternat des hopitaux de Paris, July 11, 1906, 



NON-MEDICINAL THERAPEUTIC ACTIONS 237 

and there is no reason for changing its name according to the 
purpose in view. In practice, persuasion may be substituted 
for suggestion; but the two procedures have their individuali- 
ties no matter what the purpose in view may be. On the other 
hand, the distinction set forth by Dr. Babinski may be correct 
in that a reasonable idea should be made acceptable without 
assistance of a special procedure, as is suggestion. In the 
case of a reasonable subject this is by no means a matter of 
doubt. But is it the same in the case of a patient? Is it 
true that the most reasonable idea will be fixed in his mind 
through the influence of persuasion alone? 

So long as no decisive answer is given to this question, I 
believe that it is necessary to maintain suggestion as a thera- 
peutic procedure, no matter how exceptional its application 
may be, because no one can at present assert either its ineffi- 
ciency or its superfluity. It may, perhaps, be necessary, in 
certain very exceptional instances, for developing a reasonable 
idea in a patient's mind. It is necessary, however, accurately 
to define the word suggestion which is subject to really regret- 
table abuse. It will suffice to read Dr. Bernheim's works 1 
to see that, under his pen, the word has deviated from its 
primary significance as embracing the whole of psychotherapy. 

In view of this lack of accuracy of the most commendable 
authors, one is tempted, like Dr. Paul-Emile Levy, 2 to pro- 

1 Dr. Bernheim writes in No. 16 of Bulletin medical, 1907, p. 177, that 
hysteria is "always curable by the psychic education of the subject, namely, 
by suggestion." Elsewhere he writes: "I suggest a crisis by simple affirma- 
tion." Thus, suggestion is, under his pen, synonymous sometimes with 
affirmation and at other times with education. Again, he writes that a 
simple exploration is an "unconscious suggestion." What is there that 
is not suggestion? 

2 Paul-Emile Levy, Bull, de la Soc. de V internal, des hopitaux de Paris 
November 22, 1904, March 23, 1905, September, 1906, and July, 1907. 



238 PRINCIPLES OF THERAPEUTICS 

pose that the word suggestion be eliminated from thera- 
peutics. The remedy would then, perhaps, be rather radi- 
cal; it will suffice to define the word suggestion in order to 
understand one another. Dr. F. Regnault has well shown 
that the meaning of suggestion must be limited to the fact of 
"bringing about the subject's obedience by means of simple 
commandments.' ' It is, in fact, the procedure of authority 
that characterizes suggestion; but authority impresses only 
the predisposed. Hence I conceive, for my part, suggestion 
as a procedure by which we develop certain ideas in the mind 
predisposed to accept them, by imposing them with authority} 
If reasoning is employed, then there is persuasion, no matter 
what the value of the idea may be. 

The word suggestion implies at once the notion of an imposed 
idea and that of suggestibility, viz., that of anomaly. What 
is, in fact, the meaning of suggestibility? In this connection 
also disagreement among authors is complete. According to 
some, suggestibility is a mental trouble, and is consequently 
quite rare; according to others (Liebault, Bernheim, Forel, 
Dubois, etc.), 90 to 97 per cent, of men, if not all, are of the 
suggestible kind. It is then readily conceived that, if sug- 
gestion must impose only unreasonable ideas, suggestibility 
supposes an unsound mentality. But it is remarked by the 
adversaries of this view that every person is suggestible in 

1 With this conception, how can we define autosuggestion? The latter 
is not a therapeutic procedure; it has nothing in common with suggestion 
except the fixation of an idea; but here this idea is forcibly unreasonable, 
or, at least, of doubtful correctness; since, if it was a reasonable one, there 
would be no question of autosuggestion, but of clear appreciation. In 
autosuggestion the idea is fixed either as a result of a natural disposition 
of the mind readily to accept any explanation of a sensation or of an im- 
pression more or less repeated, or as a consequence of incessantly repeated 
individual reasoning. 



NON-MEDICINAL THERAPEUTIC ACTIONS 239 

some respect, which seems to mean that every man is liable, 
at a given moment, to abdicate his sound sense and his fac- 
ulty of reasoning and passively to submit to unreasonable 
ideas. It is certain that men of considerable intelligence are 
seen to behave like illiterate primitives and obey an obvi- 
ously absurd suggestion. Have we not seen of late a minister, 
an ambassador, a commander of an army, prefer the empiri- 
cism of ignorant bone-setters to the science and experience 
of the best surgeons of the world? But we must distinguish 
momentary stumblings "by false and dazzling fires" in matters 
of which the stumbler is ignorant, and the habit of accepting 
all suggestions without discernment. Between the two states 
there are innumerable stages. 

In seeking to establish the limits of real, that is, morbid 
suggestibility, and those of common, natural suggestibility 
we find the same difficulties noted above when speaking of 
the limits of pathological and normal states. Dr. Dubois 
(of Bern) asserts that suggestibility exists in 97 per cent, of 
men; it may just as well be asserted that 97 per cent, of men 

are, if not sick, at least pathological, if one should make the 
mistake of including in this figure all those who presented 
some little imperfection, such as an imperfection of vision, 
or an inflammation limited to a mucous membrane (posterior 
rhinitis, for example) or some alteration of still less importance. 
This manner of determining things seems to me exaggerated. 
While it is undoubtedly true that any man is liable to be 
impressed or even persuaded by the statements or reasonings 
of another, whether it be a lawyer, a professor, a merchant, 
a preacher, a physician, or a political orator, and even when 
the object of this persuasion should not be absolutely reason- 



240 PRINCIPLES OF THERAPEUTICS 

able, there is no warrant for the conclusion that any man 
would accept a suggestion properly so-called. If it is admitted 
that suggestibility is a mental trouble presenting the three char- 
acters: 1. suggestion of unreasonable ideas; 2. an habitual 
mental disposition; 3. capability of being easily induced, it 
must be concluded that, after all, suggestibility is exceptional. 
As to occasional suggestibility to which any man may be 
subject in regard to ideas which, if not unreasonable, are at 
least doubtful, it cannot be considered otherwise than as a 
weakness inherent in human nature. 

Thus interpreted, suggestibility is a mental trouble and 
explains the word predisposed which we admitted in our defi- 
nition of suggestion. 

The word suggestion also evokes, as I said, the sense of 
imposed idea. Now, there is a great difference between the 
procedures of authority which is exerted with directness or 
insinuation, and those which appeal to reason and call into 
play the normal activity of the centers of consciousness. 
Suggestion which imposes an idea by appealing to blind faith, 
does no more than overcome a symptom; it is by no means 
really curative, 1 while the correction brought about by logical 
reasoning sometimes succeeds in modifying the whole frame 
of the mind, if not in a definitive manner, at least for a more 
or less long period of time. If it is evidently powerless to 
remove the original weakness, primary cause of the morbid 
disturbance, it instructs the patient, who, thus warned, 
becomes more prudent and less vulnerable. 

1 Dr. Bernheim (loc. cit.) very rightly says in regard to suggestion in 
hysteria: "It may always suppress the crises, teach the patient to inhibit 
them; but it permits the fundamental malady to subsist without the crises 
which are but an epiphenomenon." 



NON-MEDICINAL THERAPEUTIC ACTIONS 241 

Such is the result of psychotherapy in certain cases of 
psychasthenia. There is even a sort of antagonism between 
suggestion imposed and persuasion deduced from logical 
reasoning: the less capable a man is of quick and correct, 
reasoning, the more easily he gives way to suggestion. This is 
the reason that men, more inclined to reasoning than women 
are less susceptible to suggestion than the latter. Moreover 
authoritative suggestion offers this grave drawback from a social 
standpoint, that it leads to a still more exaggerated develop- 
ment of suggestibility which constitutes a state of inferiority; 
it is therefore vicious in that, in incompetent hands, it can 
overcome the symptom by diminishing the personality. Con- 
versely, reasoning, by educating or re-educating the patient's 
psychic faculties, revives the nervous dynamism, and restores 
the normal play of disturbed functions. It thus cures the 
symptom and, at the same time, strengthens the patient's 
character. Lastly, suggestion is applicable only to suggestible 
subjects, while reasoning may be developed in all persons 
enjoying the integrity of their reason. 

Without going into details, which would be out of place 
in a book of principles, we must say that authoritative sug- 
gestion cannot be more than an exceptional procedure, tran- 
sitorily applicable to hysterical subjects with a view of urgently 
overcoming too tumultuous manifestations, or to children 
whose reasoning faculty is inadequately developed, provided 
that they soon be replaced by more rational means. 

Therapeutic suggestion was formerly always obtained in a 
hypnotic state — defective and dangerous condition — since 
the subject that was accustomed to being hypnotized, be- 
came more and more hypnotizable and gradually lost the 

16 



242 PRINCIPLES OF THERAPEUTICS 

control of his personality, which he abandoned to a strange 
influence. Dr. Liebault and Dr. Bernheim have rendered a 
great service by demonstrating that hypnosis was not at all 
necessary for obtaining the effects of suggestion, and that 
this state simply served to intensify suggestibility. The 
practice of suggestion in the hypnotic state has been almost 
abandoned, and among the competent its application is 
limited to an exceedingly restricted number of cases. 

Persuasion by logical reasoning or by education of the mind 
(Pierre Janet), and above all by means of a moralizing educa- 
tion (Dubois) is incomparably superior to suggestion proper. 
This method has found an ardent propagator in Prof. Dubois 
(of Bern), who has shown, in an excellent book, 1 all the advan- 
tage that can be derived from re-education of psychic fac- 
ulties; it is the method of choice in psychoneuroses (neu- 
rasthenic, psychasthenic, and hysterical states). Its object 
is to render the patient his own master and make him un- 
derstand "the disastrous influence of fear, the noxiousness 
of discouragement, the ugliness of egotism" (Dubois). It 
requires, on the part of the physician, patience, reasoning, 
logic, memory, tact, and psychological and moral knowledge 
which never permit the patient to escape by sophism from 
the correct development of the thought. 

It was once believed that a temperament of thaumaturgy 
was necessary to produce conviction. Undoubtedly fixity 
of look, firmness of voice, physical ascendency, perhaps un- 
known exteriorized vibrations capable of affecting the patient, 

1 Dr. Dubois, "Les psychoneuroses et leur traitement moral." Paris, 
1904. See also Dr. Dubois' report to the French Congress of Medicine of 
Geneva (1908) on neurasthenic states. This remarkable work is a very 
learned complement to the book of the same author. 



NON-MEDICINAL THERAPEUTIC ACTIONS 243 

add to the psycho therapeutist's authority; but it is, above 
all else, dialectics that play the essential part; Dr. Dubois 
says even " sentimental dialectics. 7 ' 1 As in all relations 
between man and man, the physician's moral authority, 
which springs from the qualities of the mind and the heart, 
is a powerful auxiliary. "The physician's power of action," 
says Dr. Dubois, " depends upon the profundity of his con- 
viction; but in order to be profound, it must be sincere." 

The physician's qualities, however, do not always suffice; 
it is also necessary for the patient to submit to treatment, 
and endeavor to assimilate the elements of psychic educa- 
tion offered. Here intervenes the facility of adaptation, as 
necessary to 4he success of logical reasoning, as sugges- 
tibility is to the success of suggestion. This is the reason 
that women, so pliable to all forms of adaptation, are more 
readily curable than men. 

Whether by suggestion or by persuasion, it is no longer 
hoped that the spinal cord, the nerves, or certain organic 
lesions of the nervous system can be acted upon. The most 
intensive hypnotic suggestion can act neither on these or- 
gans nor on these lesions. Psychotherapy has no influence 
except on psychic troubles, and its successful intervention 
is limited to the states noted above (neurasthenia, psychas- 
thenia, hysteria), nor is it sufficient in all cases. In fact, it 
must always be corroborated by some rational bodily treat- 
ment (treatment of dyspeptic, intestinal, renal, cardiac states). 

The influence of environment and of certain adjuncts on 

1 Dr. Dejerine has also said, in the French Congress of Medicine held at 
Geneva in 1908: "The neurasthenic is not cured by syllogisms, by reason, 
but by sentiment." This is what I subsequently shall call "education or 
re-education of sentiments." 



244 PRINCIPLES OF THERAPEUTICS 

the results of psychotherapy is undeniable. For this rea- 
son, isolation, rest in bed, and overfeeding should enter 
into the scheme of psychotherapy in the beginning of its 
institution. 

Isolation, which at one time was much more practised than 
at present, sought to suppress the unfavorable influences 
exerted by the entourage, the habits, and repetition of im- 
pressions that had occasioned or prolonged the morbid state 
and those exerted by worry. It had also the advantage of 
guarding the patient against all suggestions of a nature to 
hinder the psychic action exerted by the physician. It has 
since been observed, however, that the patient's return to 
his habitual environment often gave occasion for a relapse, 
and that, on the other hand, isolation left the patient every 
liberty to confine himself to his sad ideas (Paul-Emile Levy); 
its importance is therefore much diminished. Dr. Levy is 
opposed to isolation treatment. Dr. Dubois also has given 
up isolation except in those cases where there are harmful 
family influences to be suppressed. He does not resort to 
rest in bed except in states of extreme fatigue and denutri- 
tion, when there is persistent headache and backache; nor 
does he prescribe overfeeding except in cases of consider- 
able emaciation. 

Religious influence is a psychic action seriously to be taken 
into account, no matter what the physician's opinion on 
religion may be. Religious faith is a powerful influence 
which exalts, more or less, according to the individual, the 
cerebral dynamism and aids the organism to endure the 
troubles of disease. It would be very wrong to deprive a 
religious patient of so powerful an auxiliary. One of the 



NON-MEDICINAL THERAPEUTIC ACTIONS 245 

greatest authorities on questions of psychotherapy, Dr. 
Dubois (of Bern), says: "In this state of the soul (true Chris- 
tian stoicism), alas, so rare in certain thinking circles, man 
becomes invulnerable. Feeling himself supported by his 
God, he fears neither disease nor death. He may succumb 
under the blow of a physical disease, but morally he stands 
bravely in the midst of his sufferings; he is inaccessible to 
the cowardly emotions of the neurasthenic. I have seen 
Protestant Christians accept the hardest life, the most pain- 
ful diseases, look serenely forward to their approaching end, 
even without seeking to escape their inevitable destiny by 
demanding the assistance of medicine; they knew how to 
suffer joyfully." 

Is there not here a force in the full acceptation of the 
word, and therefore a therapeutic action? I do not mean to 
say that we should resort to manifestly superstitious practices, 
or exploit the miracle that never takes place, or abuse sugges- 
tion whose dangers we have pointed out; but, as Dr. Dubois 
says: "it would be easy to profit by the cult, by religious 
holidays, to arouse fervor and invigorate in this spiritual 
life these souls weakened by material anxieties. " In a word, 
religious faith, sincere and in conformity with human reason, 
can properly be called a therapeutic action; while supersti- 
tions, puerilities, practices derived from interested or in- 
sufficient observations have nothing to do with scientific 
medicine. 

When the patient has recovered under the influence of 
psychic actions, aided by somatic treatment, it remains to 
prevent a recurrence of the trouble. This can be done by a 
nervous hygiene calculated to obviate the causes of fatigue 



246 PRINCIPLES OF THERAPEUTICS 

that had once caused the exhaustion. These causes are 
four in number, according to Dr. Dubois: physical labor, 
intellectual labor, abuse of pleasures, and, above all, emotions. 
Whoever fails to avoid them, will infallibly again fall into 
a crisis of exhaustion. 

To sum up: psychic actions are exerted by means of the 
following procedures: Suggestion: in the hypnotic state 
(of an exceedingly rare application); during wakefulness 
(seldom useful). 

Psychic education and re-education of attention, judg- 
ment, memory, moral sense, sentiments, and " dissociation 
of fixed ideas" (P. Janet). 

Adjunct influences: isolation, entourage, rest in bed, over- 
feeding, climate, configuration of the country, religious in- 
fluence, somatic treatment. 

MECHANICAL ACTIONS 

Mechanical actions are those exercised by means of the 
hands, apparatus, instruments, or position, on a passive 
subject or some part of his body — all operations free from 
bloody character. The latter condition differentiates 
mechanical from surgical operations. Mechanical actions are 
exceedingly numerous, especially if we include reduction of 
dislocations, of hernia, digital pressure in aneurysm, and, in 
a general manner, all bloodless surgical interventions. Some 
are curative (expulsion of objects arrested in the respiratory 
organs, cessation of syncope by low position of the head, 
reduction of a dislocation); others, functional (action of mas- 
sage on circulation, rhythmical traction on the tongue, intu- 
bation of the larynx); many are symptomatic (orthopedics, 



NON-MEDICINAL THERAPEUTIC ACTIONS 247 

hernia, trusses); a certain number represent reparative thera- 
peutics (washing of the bladder, dilatation of the ureter, for 
instance). Many of the mechanical actions come within the 
scope of surgery, but many others belong to the medical 
domain (tapping of effusions, blood-letting, washing of the 
stomach). Some have applications in both surgery and medi- 
cine: I refer to Bier's method. 

It is known that tubercular arthritis may be cured by pres- 
sure exercised above the diseased articulation. Recoveries 
of this kind demonstrate the usefulness of venous hyperemia; 
that is, of asphyxia exerted locally upon tubercular lesions. 
This fact must be placed by the side of the results obtained 
in pulmonary tuberculosis through dorsal decubitus, which 
perhaps is the most effective feature in the treatment of these 
patients. The fact also throws light upon the reason for the 
utter failure of attemps of treatment by over-oxygenation 
and by ozone, conceived according to theoretical views. 
Hence this conclusion that horizontal decubitus, in tubercu- 
lous subjects, acts by producing passive congestion of the 
lungs and by asphyxiating tubercular lesions. 

In fact, the rest cure is inadequate: it must be com- 
bined with rest in bed in the dorsal position. It is true that 
sanatorium treatment goes with continuous aeration, which 
seems not to agree with this conclusion; but it is to be remarked 
that this aeration undoubtedly acts by furnishing a more or 
less aseptic medium, viz., it acts by the purity of the air from 
a microbic standpoint rather than by the chemical qualities 
of the atmosphere. Sojourn in the air, without rest in the 
dorsal position, succeeds only in torpid tuberculous subjects 
who benefit through stimulation of their defective nutrition. 



248 PRINCIPLES OF THERAPEUTICS 

At any rate, it seems that this continuous aeration is not 
the most important part of the treatment, since consumptives 
recover in Paris and in great cities where the air is notoriously 
impure. Cure obtained empirically in stables is in favor of 
the preponderant importance of the asphyxia, as compared 
to that of the purity of the air. 

The mechanical means employed in therapeutics may act 
on the whole body, on the general circulation (blood-letting, 
transfusion, massage), on local circulations (lowered position 
of the head, massage, Bier's method, horizontal decubitus, 
elastic stockings, digital and instrumental pressure), on the 
organs (girdles, hernia bandages and trusses, pessaries, washing 
of the stomach, intestines, bladder, and nasal cavities, dental 
pro theses) , on functions (artificial respiration, rhythmical trac- 
tion on the tongue, intubation of the larynx), on canals 
(dilatation of the urethra, lachrymal passages, cervix uteri), 
on the . skeleton (orthopedia, mechanotherapeutics), on 
pathological products (puncture of effusions and of edemas), 
on normal products retained in their reservoirs (catheterization 
of the ureter, tapping of the bladder, washings, evacuation of 
the uterus filled with blood-clots). It is seen by this long 
enumeration that mechanical actions are of capital importance 
in therapeutics. 

PHYSICAL ACTIONS 

Physical actions are those exercised by means of. a physical 
agent: heat, cold, electricity, radium, pressure of air, light 
and color, magnetism, application of metals. Among these 
actions, some have been seen among hygienic actions, since, 
among the environmental elements there are some physical 



NON-MEDICINAL THERAPEUTIC ACTIONS 249 

ones, such as temperature, pressure, and light. However, 
it is proper to distinguish between the elements such as are 
offered by nature and can be realized without getting far 
away from this natural state, and these same elements ab- 
stracted by physics. Thus temperature, an element of cli- 
mate and environment, belongs to hygiene, while the high 
temperatures of cauteries (thermo- and galvano-) are more 
especially physical actions. The reaction produced by 
cold water is an application of the hygienic order; but cold 
obtained by evaporation of ethyl chlorid or by some refriger- 
ant mixture, for producing local anesthesia, is more exactly 
of the physical order. It is infinitely probable that natural 
light has a very marked action on the organism, action which 
has not yet been precisely understood and utilized by thera- 
peutics, no doubt because the respective quantity and the 
special action of caloric and of chemical rays in various coun- 
tries has not yet been sufficiently studied; on the other hand, 
the luminous elements, isolated by physics, have endowed 
therapeutics with very powerful means. 

Among the physical actions there are three that have as- 
sumed in recent years a considerable extension. First, radium- 
therapy, and particularly the very penetrating action of X-rays 
which have manifested a remarkable curative action on 
angiomata, especially in children, on superficial epitheliomata, 
and on certain chronic lichenoid eruptions and chronic 
eczemas. 

Radiotheraphy, now somewhat less employed in the treat- 
ment of epithelioma, preserves all its curative value in the 
treatment of sycosis, certain kinds of lupus, and in the various 
forms of lymphadenia and leukemia. 



250 PRINCIPLES OF THERAPEUTICS 

Electricity, in the midst of deceptive promises, has given 
such results in a certain number of cases that it would be hard 
for us to dispense with its services. All its forms are utilized 
(static, galvanic, faradic, high frequency, sparks). The cases 
in which it has proved useful are too numerous to be men- 
tioned. It also contributes to the accurate appreciation of 
diagnosis and prognosis of lesions of the nervous system. 

The cure of lupus by phototheraphy (Finsen) is one of the 
finest applications of physics to therapeutics. 

Let us simply mention also the modifications of air pressure 
by means of apparatus the application of which constitutes 
pneumotherapy or aeropiesis, or aeropiesotheraphy. 

Musicotherapy also is now spoken of. 

This summary enumeration suffices to show the power 
which knowlege of physical agents has placed in the thera- 
peutists hands. 

SURGICAL ACTIONS 

It is superfluous to consider here surgical therapeutics, 
which is of so special an order. 



CHAPTER XI 
METHOD IN THERAPEUTICS 

Elements of certainty in biology and particularly in therapeutics — Facts, 
interpretations, and opinions — Simple facts, composite facts and relations — • 
Reasoning, hypothesis, theory — Appreciation of the value of a therapeutic 
fact — Methods for studying the means of therapeutics — Observation and 
experimentation — Clinico-therapeutic observations — Statistics — Summary. 

I have now reached the most difficult part of my task: 
to lay down the principles of a method as I conceive it. Aware 
of its imperfections, it is not without some hesitation 
that I venture to do so, but I believe that therapeutics 
will not progress steadily and render the services expected 
unless it is equipped with precise and undisputed methods. 

THE ELEMENTS OF CERTAINTY IN BIOLOGY AND PAR- 
TICULARLY IN THERAPEUTICS 

Therapeutics is built up little by little with elements of 
varied value, which are: facts, reasonings, hypotheses, and 
theories. Well-observed facts and correct reasonings alone 
engender certainty, that is, science. Hypotheses and theo- 
ries intervene only as provisional means. Certainty itself 
is understood from the human standpoint, namely, it is seldom 
absolute, and it is often necessary to content oneself with 
probabilities which offer guarantees practically sufficient. 
This distinction, which results from the complexity of the 
objects of our studies, will be more apparent in the light of 
a few illustrations. 

251 



252 



PRINCIPLES OF THERAPEUTICS 



Although the imperfection of our means of information 
may sometimes lead us to record errors, the importance of 
probability is not to be undervalued. Probability is often 
a necessity in therapeutics and even constitutes the only 
means of appreciation to which resort can be had in the 
establishment of prognosis, without which there is no pos- 
sible therapeutic judgment. Probabilities are admitted even 
by mathematicians. "It is proper/' remarks d'Alembert, 
"not to confine researches only to objects capable of demon- 
stration, but to preserve the flexibility of the mind, by not 
keeping it all the time turned toward lines and calculations, 
by moderating the austerity of mathematics by less severe 
studies and to accustom oneself to pass without trouble from 
light to twilight;" however, "it is all the more necessary to 
have rules for conducting oneself, since the art of conjecture is 
imperfect in itself" Are not these words particularly suit- 
able for Ijherapeutics? Do they not point out its stumbling 
block? Too exclusively scientific a 'mind disdains these con- 
jectures, and the mind that is devoid of scientific spirit aban- 
dons itself to their mercy. It is above all else due to the 
lack of rules that therapeutics is infested with parasiticism 
which often prevents due appreciation of the value of ac- 
quired truths. 

To what requirements then must a fact respond to en- 
gender certainty or a probability that may be considered 
as practically sufficient and scientifically acceptable? 

At first sight, it seems as though nothing is easier than to 
appreciate a reality, yet it not infrequently happens that, 
in current speech or in writings on medicine, simple inter- 
pretations or even mere impressions are designated under 



METHOD IN THERAPEUTICS 253 

the name of facts. The point of departure being uncertain, 
it is no wonder that the conclusions drawn therefrom are 
doubtful or inaccurate. 

FACTS, INTERPRETATIONS, AND OPINIONS 

An absolutely certain manner of being or of acting alone 
deserves the name of fact. Certainty is the characteristic of a 
scientific fact. The simpler the fact, the more readily this 
characteristic will be realized. Every complexity implies a 
set of conditions the elements and relations of which are not 
always accurately known: now, a single unknown element 
suffices to lessen certainty, and a single inaccuracy is enough 
to annihilate it. For this reason interpretation is of doubtful 
value, since it strives to attribute to facts undue importance, 
with a view of connecting them with their cause or penetrating 
into their mechanism. It would be exact, if each element 
was certain, and if the relations that are said to exist between 
these elements were also exact; but in reality these conditions 
of certainty are difficult to realize. 

Certainty is acquired either through an exact and controlled 
impression on the trained senses, or through reasoning which 
does not err at any point. Certainty requires that the fact 
should bear in itself or in the facts accompanying it, its charac- 
teristic or its elements of differentiation, without which the most 
perfect senses would be powerless to characterize or to differ- 
entiate it. A simple fact meeting these conditions, or a 
simple reasoning give a satisfactory certainty, provided the 
precise idea revealed by the senses or reasoning is not over- 
estimated. These conditions easily realized in mathematical 
or even physico-chemical sciences, in which verification and 



254 PRINCIPLES OF THERAPEUTICS 

control can generally be reproduced at will, are far less fre- 
quently united in biological sciences, which are more com- 
plex. Their realization is a matter of particular difficulty 
in therapeutics, because, in this science, complexity is increased 
by the pathological element, by the difficulty of appreciating 
the results of modifications induced in the suffering organism, 
arid by the difficulty of control. For this reason clinical obser- 
vation that would appreciate by itself (that is, without the 
aid of experimentation and the laboratory), in their complex- 
ity, both the properties of therapeutic agents and the 
effects of these agents in a given case, would be, in 
general, a procedure of investigation filled with uncertainties. 

The contingent character of clinical facts does not result 
solely from the difficulty of distinguishing fact from fancy; 
it also proceeds from the observer's personality. The value 
of an observation is measured by that of the observer; this 
fact ruins the so-called observation of incompetent observers 
who see, but cannot discern. If the value of a fact of obser- 
vation is subordinated to the eye that sees, the ear that hears, 
the hand that touches, the conscience that affirms, it is evi- 
dent that a clinical fact can compel conviction and constitute 
an utilizable document only when it is accompanied by suffi- 
ciently accurate and numerous details demonstrating the 
observer's competence and thus enabling others to criticize 
the fact. Certainty can be derived neither from an inter- 
pretation nor from an opinion, no matter how highly 
authoritative. 

It is, therefore, always necessary carefully to distinguish 
facts, interpretations, and opinions, and to offer to others the 
means of distinguishing them. 



METHOD IN THERAPEUTICS 255 

Simple Facts, Composite Facts, and Relations. — First 
of all, it is important fully to realize that the facts of medicine 
are complex, in order to acquire the habit of subjecting even 
the simplest elements to careful analysis and criticism. 

A simple fact is nothing else than the statement of a thing 
existing. It can be only a point of departure, for, in order 
to derive from it a teaching, one is led to connect it with 
another statement, i.e., to establish a relation between the 
two. This relation constitutes a new fact of greater complexity, 
but comparatively very simple, and very certain, provided 
that the two elements composing it be tliemselves very certain, 
and that their relation be constant. Let us take, for example, 
the convulsivant action of strychnin. The facts proving it 
represent the constant relation between two simple elements: 
1. administration of the poison; 2. convulsions. 

Sometimes one of the terms of a compound fact or rela- 
tion eludes; we know, nevertheless, that it does exist: the 
false membrane of diphtheria is related to the development 
of a bacillus well known to-day; but, when this bacillus was 
unknown to us, we were certain of the existence of the term it 
represents; but we were seeking it through hypotheses and 
theories. The second term, the false membrane, falls under 
the sense of vision. To-day when we state the fact of diph- 
theria, we announce a relation between Loeffler's bacillus and 
the existing false membrane. 

A therapeutic fact is always very complex. In fact, it ex- 
presses a relation between the medication to which a patient 
has been subjected and the result obtained. But each of 
the elements of this relation is itself extraordinarily complex. 

The first term includes in itself two elements, one of which 



256 PRINCIPLES OF THERAPEUTICS 

is the diagnosis of the disease, the other is the medication 
employed. Now, the first one already carries a very serious 
difficulty from the standpoint of the certainty of the scientific 
fact. 

When it is stated concerning a patient that he is suffering 
from typhoid fever, for instance, no fact is thereby enunciated 
if the diagnosis is not certain. This diagnosis is usually 
founded on a set of symptoms and signs which, taken sepa- 
rately, are inadequate to fix any differentiation. The same is 
true of many cases. Therefore, that which gives to the diag- 
nosis of a disease the value of a probability equivalent to a 
clinical certainty, such as is generally accepted, is the union, 
in the same subject and in an habitual chronological order of 
occurrence, of symptoms and signs some of which have the 
character of certainty and others, interpreted in the light of 
the former, assume the character of the greatest probability. 
In the absence of signs of certainty, everything is interpreta- 
tion, hence errors. To take up again the illustration of typhoid 
fever: in this disease, much importance is rightly given 
to the rose-colored spots. A rose-colored spot would possess 
the value of a fact of certainty and would impart this charac- 
ter to the diagnosis, if it were certain; but, in reality, it has 
nothing surely characteristic of itself; it is differentiated by 
its seat, the date of appearance, and the symptoms in the midst 
of which it appears rather than by its own characters. Hence 
it is not infrequently interpreted as a commonplace papula 
or one of sudoral origin, and conversely. 

The differentiation of typhoid symptoms and signs are so 
far from accurate that descriptions of epidemics of this dis- 
ease have been seen under the title of influenza of the ab- 



METHOD IN THERAPEUTICS 257 

dominal type, and that in unnumbered instances typhoid 
has been confounded with influenza or malaria or meningeal 
tuberculosis or Malta fever. All these mistakes are accounted 
for by the circumstance that the reasons set forth in sup- 
port of a diagnosis represented interpretations and not facts. 
Generally these interpretations cannot deceive the experi- 
enced clinician who knows how to profit by experience and 
by accuracy of sense impressions in appreciating the value 
of observable facts; but they mislead more easily those who 
love paradox and contradiction and fanciful views. At all 
events, it is interpretation substituted for certainty that 
accounts for the surprises at the autopsy. 

But in the midst of discussions and interpretations, as 
soon as a simple fact, carrying an adequate element of dif- 
ferentiation and observed by a person of undeniable com- 
petence, is brought in, diagnosis becomes certain and takes 
the character of a fact. Thus the agglutinative power of 
blood serum on a fresh culture of Eberth's bacillus diluted 
to one-fiftieth makes the diagnosis of typhoid certain, be- 
cause the relation between the agglutination of the special 
culture and the serum of typhoid patients is established by 
the recognized constancy. Pathognomonic signs, when ex- 
actly perceived by the senses, render the same service. 

When there is an error, it is because some important ele- 
ment in the patient's observation has been overlooked. I 
remember to have seen, in some foreign clinics, a patient 
who, with fever, gastro-intestinal disturbances, tympanites, 
and pain on pressure in the right Iliac fossa, presented a posi- 
tive sero-reaction. It was taken to be a sure case of typhoid, 

but the development proved it to be one of appendicitis. 

17 



258 PRINCIPLES OF THERAPEUTICS 

The sero-reaction was due to the fact that the patient had 
suffered from typhoid fever a few months before. There is, 
therefore, danger of error, even in the presence of a fact of 
certainty, if some element of diagnosis is overlooked. This 
shows how prudent one must be before giving a clinical ob- 
servation the value of a fact acceptable to science. 

What is to be said of the cases in which a simple opinion 
or mere interpretation is offered as a fact? I have dwelt 
upon the necessity of an exact diagnosis as an element of 
therapeutic reality, because in a great number of observa- 
tions the author's diagnosis is simply indicated without any 
proof to support it. 

There are, for instance, observations taken from a thera- 
peutic standpoint, in which it is simply stated concerning a 
patient that he was tuberculous. In so doing, a writer enun- 
ciates no fact for his reader, but simply expresses an opinion 
that has. by no means the value of a scientific fact. If it is 
further stated that the patient had hemoptysis, a very slight 
presumption of probability only is added thereby, since the 
hemorrhage in question may have had an origin other than 
a blood-vessel open by a tubercular lesion. It was neces- 
sary to show that this hemorrhage was certainly a hemop- 
tysis for such and such reasons of development, color, aspect, 
concomitant disturbances in circulation and respiration, 
fever, and parallel absence of disorders on the part of the 
stomach and upper aero-digestive passages. When the cer- 
tainty of hemoptysis is furnished, the presumption of tuber- 
culosis is already much stronger, because one of the terms 
of relation which constitutes the fact is more precise; but if 
the description of physical signs and symptoms usually found 



METHOD IN THERAPEUTICS 259 

in tuberculosis is given, then the presumption becomes a 
strong probability and, in the majority of cases, sufficient . 
The absolute certainty is derived from direct finding, by a 
competent man, of Koch's bacillus in the sputa, because it 
secures one of the terms of relation which constitutes the 
fact of tuberculosis. 

Even in this case, the importance of the presence of the 
specific bacillus must not be exaggerated, since there is yet 
the other term of the relation to be looked for, that is, the 
patient's pathological state. In fact, if the patient should 
at the same time present phenomena which are not habitually 
encountered in tuberculosis, it would be an error to believe 
them to be surely due to tuberculosis, merely on account of 
the presence of tubercle bacilli in the sputum. It is even 
necessary, in certain cases, to disregard this element, if we 
clearly see the development of some other morbid state in 
the tubercular soil (syphilis, cancer, typhoid fever, etc.). 

The first element of a therapeutic fact, diagnosis, is, then, 
difficult to appreciate, and one can never be too prudent in 
its affirmation. The second element, the treatment employed, 
is easy to appreciate only in the event of specific therapeutics. 
In the majority of other cases many prescriptions are formu- 
lated and it is a matter of difficulty to distinguish the most 
efficacious among them. Lastly, the relation between the 
progress of the disease and its treatment constitutes a third 
element which is the most difficult of all to affirm. 

We shall attempt to say how these difficulties can be reduced ; 
it is sufficient for the moment to show that it is necessary to 
take into account three groups of elements which will acquire 
the value of certainty only when all the simple elements con- 



260 PRINCIPLES OF THERAPEUTICS 

stituting them have been dissociated and subjected to the 
test of critical examination. The latter alone will enable one 
to substitute a scientific characteristic — certainty, for a 
vague impression or for a contingent affirmation. 

Value of Reasoning, of Hypothesis, and of Theory. — 
An impeccable reasoning gives the same certainty as the obser- 
vation of facts: mathematics is the evidence of this. But 
reasoning has this value only when it is applied to simple ideas. 
When the problem is complicated, it becomes easy to overlook 
one of its terms; and then reasoning leads to error. In thera- 
peutics the great stumbling block is to start from ill-observed 
facts, inadequate conceptions, and imaginary views taken for 
realities. For instance, thirty years ago, when a nursling 
suffered from acute diarrhea, it was thus reasoned: the 
woman's milk is the one most easily digested by an infant; 
the little patient is therefore to be nursed at the breast, and 
if it already is, it must be at longer intervals. As the proce- 
dure was insufficient to cure, resort was made to medicines 
(evacuants, ipecacuanha, opiates, bismuth, enema, etc.), 
which often only aggravated the evil. The reasoning was 
wrong at its basis. The woman's milk is well digested by an 
infant when its stomach is healthy; but the acute diarrhea 
of the suckling is more commonly a gastroenteritis than 
an enteritis. Then the milk, even woman's, is no longer 
digested, and the medicines intensify the irritation of the 
stomach. It is to-day concluded that the first indication is 
to give rest to the digestive organs, by giving nothing but 
water (sterilized), necessary to the child. 

And yet therapeutics must be reasoned in order not to be 
often useless or harmful; and it must confine itself to simple 



METHOD IN THERAPEUTICS 261 

reasoning bearing on certain facts. A therapeutist can never 
be too scrupulous in his observation of facts, in his criticism 
and control of those that are presented to him, in order to 
guard himself against infatuation, hazardous theories, skep- 
ticism, and incessant variations. 

Theory should not be confounded with reasoning: the latter 
proceeds with elements of certainty, while theory, starting 
from laws and certain facts, seeks through them to explain 
other certain facts the mechanism of which is unknown, but 
by the assistance of uncertain and simply possible or probable 
data. Such, at least, is the sense I would give to scientific 
theory, the only one practically acceptable. But there are 
other manners of understanding the word theory. It is some- 
times made the designation of speculative knowledge, without 
application. Theories of this kind become exceedingly dan- 
gerous when the attempt is made to apply them anyhow. A 
theory is also said to be a scientific ensemble resulting from 
a series of laws with which we connect facts of observation. 
This manner of comprehending theory approaches ours, but 
it is more general and has no immediate application. 

Theory, as I understand it, explains; it gives no certainty. 
It is not anti-scientific, however, when it is supported by facts, 
some certain and some probable, and by correct reasoning, 
but it is often suspicious because, by definition, theoretical 
reasoning is not responsible for the certainty of all the elements 
of a biological problem. In therapeutics, a good theory, 
from which is demanded only what it can give, may have its 
usefulness; but its elements would generally be so complex, 
and its abuses so easy, that it is preferable to give only a very 
restricted place to this mode of information. The interest 



262 PRINCIPLES OF THERAPEUTICS 

of the theory is to give satisfaction to the mind, to furnish a 
means to retain facts by binding them together, and to aid 
in perceiving new facts, intermediary to those which serve 
as the basis of the theory. 

Hypothesis is a procedure which, starting from uncertain 
conceptions, but rendered probable by general ideas upon 
which they are founded, lead, by way of reasoning, to con- 
ceptions equally uncertain, which we are seeking to verify 
or demonstrate. It is evident that if the point of departure 
is exact and the reasoning correct, hypothesis is most likely 
to terminate in a new scientific fact. But the danger is in 
starting from a possible error. There would be no other harm 
than loss of time if the verification of hypotheses was alone 
sought; but in therapeutics the verification is so very difficult 
that one may fall into error in very good faith. The pro- 
cedure is therefore suspicious in itself; it becomes dangerous 
by the abuse the creators of new remedies make of it. What 
chances of utility could a therapeutic procedure have, that is 
inspired by some conception on the origin of life of which we 
know nothing, or by some other notion equally fantastic? 

For all these reasons, therapeutics in reality rests upon the 
knowledge of facts and of relations acquired either by obser- 
vation or by experimentation, which facts and relations are 
utilized to fulfil the indications revealed by examination of 
the sick. These indications are themselves established by 
the appreciation of observed organic and functional modi- 
fications. Reasoning intervenes to connect with one another 
the ideas relative to remedies and to the sick. It enables 
us to learn whether the medication is to be nosocratic, organic 
and functional, symptomatic or restorative, and, thereby, 



METHOD IN THERAPEUTICS 263 

the service that may be expected from it. These principles 
having been laid down, how are they to be applied to the 
study of therapeutics? 

APPRECIATION OF THE VALUE OF A 
THERAPEUTIC FACT 

When we endeavor to appreciate, in a clinical observation, 
the therapeutic influence of remedies, we encounter great 
difficulties. We are, in fact, to compare the development 
of a morbid state, artificially modified by remedies, with 
what this development would have been if left to its spon- 
taneous course, and, moreover, to establish the respective 
value of the different parts of the treatment. There is al- 
ways, therefore, a hypothetic term in the appreciation of a 
therapeutic influence. To give this term the greatest chances 
of probability is the first condition to fulfil. Contrary to 
the physician who, in the presence of a morbid state, be- 
lieves himself obliged to combat each and every anomaly pres- 
ent I believe that the first endeavor should be, as I have 
tried to show in the chapter on medicinal opportunity, to an- 
alyze these anomalies, to establish their probable prognosis, 
and to strive to modify this prognosis, when it is unfavor- 
able, much more than the anomaly itself, which may very 
easily be acceptable. It is on this condition alone that one 
can speak of improvement or cure. 

I shall subsequently speak of the necessity of fixing the 
probable diagnosis, if we desire correctly to appreciate the 
value of a therapeutic means. But when the prognosis is 
established, all the difficulties of the situation will not have 
been overcome. 



264 PRINCIPLES OF THERAPEUTICS 

The therapeutist has in view the recovery of the patient 
or a favorable modification of his state. Now, it is not al- 
ways easy to tell at what moment a patient is cured or has 
improved. The fact is comparatively easy in an acute dis- 
ease, which is declared to have ended when all morbid symp- 
toms have vanished and when the pathological development 
has terminated for a time sufficiently long to leave no room 
for fear of a relapse or complication. But in the case of a 
chronic disease (tuberculosis, cancer, syphilis) the criterion 
of cure is often lacking. At times, it is utterly impossible 
to affirm the recovery. However, when, after the lapse of 
a time varying with the disease, the health is found quite 
satisfactory, all abnormal phenomena having disappeared or 
seemingly immobilized at a definitive phase, a patient 
formerly suffering from a chronic disease may be considered 
as practically cured. This is not the absolute scientific 
certainty; it is probability with which one has to be con- 
tented. To require more would be denying the possibility 
of practical conclusions. 

These difficulties have obliged therapeutists not to be con- 
tented with clinical observations, but to seek, outside the 
sick, the reasons of activity of therapeutic agents. To this 
effect they produce in animals diseases similar to those of 
man, and study upon them the effects of therapeutic agents 
which are supposed to be useful; or they seek experiment- 
ally to establish the influence of a substance presumably 
favorable on a pathological phenomenon taken by itself 
(pain, sleep) in the hope that they may be able to apply the 
observed results to the sick man. 

Therapeutics has not in view cure or amelioration alone; 



METHOD IN THERAPEUTICS 265 

it takes into consideration also the duration of the disease and 
of convalescence, the gravity of symptoms, and the develop- 
ment of complications and relapses. 

METHODS FOR STUDYING THE MEANS OF THERAPEUTICS 

All the methods that concur in establishing facts concerning 
therapeutics may be divided into two types: observation and 
experimentation. 

Observation and Experimentation. — Observation has 
preceded experimentation. When the latter came into being, 
it suddenly gave an extraordinarily fecundating impulse to 
entire biology. Proud of the certainty it conveyed by sim- 
plifying the object of its studies, it scoffed at observation, 
contemplative form of science, as CI. Bernard called it; while 
experimentation would be its explanatory and conquering 
form. For a long time experimentation was thus opposed to 
observation. In reality, however, experimentation is nothing- 
else than observation of facts purposely simplified by a skil- 
ful contrivance of study. There is, therefore, no reason for 
establishing an opposition between the two methods. Both 
are utilizable and of mutual assistance. 

When observation can be simple (differentiation of patho- 
logical products by means of various methods of staining, 
observation of a pathogenic sign, characteristic chemical 
reaction), direct observation offers, in regard to certainty, 
the same value as experimentation, and it has over the latter 
the advantage of taking facts just as they are presented by 
nature. 

Moreover, observation, provided it is accurate, has always, 
in pathological biology, the last word to pronounce as regards 



266 PRINCIPLES OF THERAPEUTICS 

experimentation. In fact the latter places itself in conditions 
determined and simplified, but artificial. If this is a cause 
of scientific certainty, it is at the same time a reason of infe- 
riority in the face of the complex problems of pathological 
biology. The complex facts which observation does not 
succeed in mastering, are just as inaccessible, in their com- 
plexity, to experimentation. The latter can be exact only 
under the conditions of simplicity which it creates voluntarily; 
but, by thus simplifying, it gets away from reality, sometimes 
quite far, and loses from the standpoint of truth what it gains 
from that of accuracy, so that its results cannot always lend 
themselves to precise application. On the other hand, the 
conscientious and exact observer, who has a clear idea of 
the value and the conditions of certainty of facts, considers 
the real problem, and he alone can be the last judge of the 
experimenter's conceptions. 

How often have we seen very alluring deductions, derived 
from experimentation, fail when applied to man? Did not 
simple observation, contemplative though it was, here affirm 
its superiority over the conquests of experimentation? It 
is particularly tuberculosis that has caused these deceptions. 

The main value of observation is to study, to contemplate , 
if you like, the problem as it is put by nature, in all its com- 
plexity and all its difficulty. These conditions are often 
such as to render the problem inexplicable, but they as 
often produce first-class results. 

Direct observation of itself is capable of establishing cer- 
tain scientific facts or facts of adequate probability, practi- 
cally equivalent to certainty. Was experimentation neces- 
sary to learn how to overcome syphilitic manifestations and 



METHOD IN THERAPEUTICS 267 

malaria; to establish the therapeutic value of digitalis in 
asystole; of colchicum in gout; to profit by the active force 
of mineral waters; to make good use of massage and hygiene? 
In another order of ideas, did Davaine and Laveran need pro- 
cedures more complicated than observation for discovering 
and describing, one the anthrax bacillus, the other the hema- 
tozoon of malaria? 

By patience, precision, and control, the observer often suc- 
ceeds finally in clearing up complex facts and establishing 
simple utilizable facts. He has always at his command the 
resources of experimentation for the study of doubtful points, 
in order to give them this necessary character of certainty 
and to complete the results of observation. Thus there was 
divergence of opinion as to the contagious character of 
tuberculosis. This character was surmised, but had not been 
ascertained. Villemin established by experimentation the 
fact of inoculability, which lent reason to the views of the 
advocates of contagiousness. In order not to overestimate 
the bearing of these studies, it suffices simply to conclude 
that tuberculosis is inoculable and contagious. To go further 
and state that tuberculosis is always contagious and in- 
oculated, would be to exceed the facts. From the purely 
therapeutic standpoint, the clinician sees, by observation, 
the marvelous influence of digitalis on asystole. But there 
is one thing he does not know: that is, the relation of this 
remedy and the modifications of the functional activity of 
the heart. He asks it from experimentation which, by 
diverse procedures, succeeds in determining the action of 
digitalin, respectively, on the myocardium and on its 
innervation. 



268 PRINCIPLES OF THERAPEUTICS 

Observation, often somewhat fantastic in past centuries, 
was seemingly eclipsed for a moment by the brilliant dis- 
coveries of experimentation, at an epoch when, by means 
of a new technic, discoveries were easy to it. Its efforts 
are to-day reduced to ascertaining certain points at the request 
of observation; while observation, enlarged by the new technic 
of the laboratory, accustomed to accuracy by the teachings 
of experimentation itself, as well as by the example of errors 
to which lack of precision may lead, has resumed its march 
forward to become preponderant. Its drawback is that 
it can be put at the disposal of the first comer who observes 
with ill-trained senses, or who is led by fanciful views or reason- 
ings, and too often by reasons of personal interest. 

Whatever the importance of observation may be, the thera- 
peutist cannot afford to dispense with experimentation, since 
it is necessary for him to take into account the elective actions 
of medicines, of the effects of this selective character, and 
of the physiological and toxic actions of remedies — facts which 
experimentation alone can establish. However, it is to be 
remarked that, as experimentation bears on animals, the 
latter's reaction implies only very approximate conclu- 
sions in the applications to man. Experimentation does no 
more than determine the sense of this reaction, and not 
even this with absolute certainty. 

It is to be recognized, however, that experimentation ac- 
quires an incontestable superiority and is capable, of leading 
to remarkable results, when animals can successfully be inocu- 
lated with the germs of our diseases and the opportunity thus 
offered to study on them the activity of curative agents. 
Then it remains for clinical observation to confirm in man 



METHOD IN THERAPEUTICS 269 

the results announced and to record the practical value of 
the remedies. 

I shall subsequently endeavor to determine the relations 
between a therapeutic effort and its effects. 

Although there can be no uniform therapeutic method, 
because of the diversity of the material of therapeutics and the 
difference of purpose in veiw, there are general methods and 
rules applicable to the great majority of cases. These alone 
I shall consider. 

Whenever a medicine is to be prescribed, it is indispen- 
sable to know: 1. The minimum dose capable of killing; 
2. the direct action on the tissues (local action); 3. the tissues, 
organs, and functions that will undergo the selective action; 
4. the functional modifications produced by harmless utiliz- 
able doses; 5. the effects observed in man by the employ- 
ment of doses appropriate to his susceptibility. This knowl- 
edge must be derived from established facts, acquired by 
experimentation on animals and by observation on man. 

The experimental study of the minimum fatal dose will, 
of course, give no exact idea of that which might cause death 
in man. Nevertheless, it is an indispensable element of the 
fear which must guard the practitioner against imprudent 
dosage of active medicines. Unfortunately, the practical 
toxicity can be established only by toxicology and subse- 
quent observation of accidents. There are accidents that 
can by no means be anticipated. How can anyone suspect 
that prolonged employment of sulphonal or trional will pro- 
duce fatal accidents unless he has witnessed such accidents? 
Nor is there any reason to anticipate the depressive action 
of antipyretics upon certain febrile patients, according to 



270 PRINCIPLES OF THERAPEUTICS 

the physiological action of these medicines. How could 
atoxyl be suspected of producing amaurosis? These illus- 
trations have a salutary and very general bearing: they dem- 
onstrate the necessity of avoiding all active and repeated 
aggression on the human organism, particularly when the 
latter is already rendered more impressionable by disease. 

The complete pharmacodynamic study of all medicines is 
not indispensable for the practising physician. The sum 
of knowledge which he should possess is so very consider- 
able that there is advantage in making a distinction between 
the most indispensable ones and those which might possibly 
be dispensed with. From this point of view it is certain that 
nosocratic medicines may be utilized with the summary 
of knowledge indicated above. Organic and functional 
medicines require a more profound knowledge of the func- 
tional modifications they can bring about and, as much as 
possible, -of the mechanism of these modifications, which ne- 
cessitates also a knowledge of the elective action of these 
remedies. But it is by no means indispensable to know 
everything about the action of toxic doses on animals. 
Symptomatic therapeutics necessitates more particularly a 
knowledge of electivities and of effects of habituation, of toler- 
ance and intolerance, whether immediate or tardy. Lastly, 
reparative therapeutics must possess, in addition to indis- 
pensable general ideas, very exact experience as far as pos- 
sible on man, the latter being submitted to a diet and labor 
strictly identical during and after the use of the medicines. 

When first offered to physicians, few medicines have been 
subjected to the series of studies indicated above. Among the 
very important ones there are some the fatal dose and tox- 



METHOD IN THERAPEUTICS 271 

icity of which are hardly known; others whose physiological 
action has scarcely received any serious attention; still others 
are offered under the cover of a more or less ingenious or 
fanciful hypothesis or physico-chemical deductions (formic 
acid) or bacteriological or opotherapic suppositions impos- 
sible to control. 

When invited to try a product, we practitioners ask, first 
of all, that it be rational; viz., that we may have scientific 
reasons for taking it seriously. In order to end the invasion 
of worthless remedies and specialties, physicians should, as 
a matter of principle, refuse to prescribe a medicine until it 
has fulfilled the conditions of previous studies described above. 
The task of studying on a patient the effects of a medicinal 
substance is already difficult enough without undertaking it 
in the absence of good reasons, even when this substance is 
offered as a harmless one. Our mission is to take care of pa- 
tients; it is by no means that of making a reputation or 
fortune for manufacturers, no matter how commendable 
they may be. When they say, "Try it anyhow, it is 
harmless," we must answer that we try only what to us 
appears to be useful. 

After acquiring this preliminary information, there remains 
to be known (or to be determined in the case of new medi- 
cines) the therapeutic value of the remedies. That clinical 
observation alone, in spite of its imperfections, can prove 
this value, is incontestable. But its imperfections are of a 
nature to impose rigid rules. 

Clinical Observations from the Therapeutic Stand- 
point. — Clinical observations relative to therapeutics may 
be divided into three groups: 



272 PRINCIPLES OF THERAPEUTICS 

1. Some constitute no more than valueless impressions. 
It is not sufficient, in order to prove the therapeutic value of 
a remedy, to say that, prescribed in such and such a case, it 
worked admirably and the patient recovered: post hoc, ergo 
propter hoc has no demonstrative value whatever. And yet 
no other proof is to be found in numerous pamphlets and 
even entire books that are being circulated, and which report 
hundreds of so-called observations! Numbers add no more 
to the presumption of utility of a medicine than ciphers 
added one to another constitute a figure. A single observa- 
tion well made is of more value than a thousand of these 
pseudo-observations. 

2. In another category the observations are grouped in 
the form of more or less comprehensive statistics, more or 
less methodically subdivided. Their value is that of the 
facts composing them; this contingency is a feature of inferi- 
ority in the method. Statistics are not to be ignored, however. 
I shall subsequently speak of the conditions capable of lending 
undeniable value to them. 

3. A third group is made up of more or less detailed obser- 
vations. Their value is subordinated to the kind of disease, 
to the value and conscientiousness of the observer, and to 
the care the latter has taken accurately to note the outcome 
of his observations. This group deserves special attention. 

It seems that, if clinico-therapeutic observations were made 
according to a rational method, they would powerfully aid 
to establish the value of therapeutic procedures. Unfortu- 
nately, many of them are inadequate. Some fail to lay down 
the diagnosis with an accuracy sufficient to render it indispu- 
table, many neglect exactly to determine the state of the 



METHOD IN THERAPEUTICS 273 

organs and functions; even the symptoms and signs receive 
sometimes only slight notice. A simple epithet characterizes 
an important phenomenon. I could cite a long work in the 
observations of which expectoration has been simply appre- 
ciated by the epithets, good and bad. Seldom, if ever ; is 
the probable prognosis formulated. It is certain, however, 
that the key of a therapeutic observation is in the prognosis. 
It is in the name of clinical observation that this or that 
substance periodically becomes for a time a panacea, which 
often misleads physicians through patients who have been 
affected by the suggestion of advertisement. Without speak- 
ing of the transitory celebrity of more or less fanciful products, 
we may well recall the favor of the public and of physicians 
for Brown-Sequard's fluid, and then for antipyrin, the 
glycero-phosphates, the raisin ferment, the X-rays, the high 
frequency currents, the alkaline formiates, and many others. 
The panacea of the day is marine serum or sea-water. Will 
the hypothesis that has inspired the idea, and according to 
which animal life originated in sea-water, enjoy more success 
than the one according to which the first organized body that 
came out of the chaos of elements should be formic acid? 
Perhaps. Not by reason of the fundamental hypothesis 
itself, which is contestable from a scientific point of view, but 
because the therapeutic procedure inspired by it contains 
in itself a previous procedure well studied, active, and rational, 
which consists in the injection of physiological salt water. 
That, after all, simple salt water is too primitive in its com- 
position, and that the artificial serums with a complex miner- 
alization more closely approach the blood composition and 
disturb the former less than the fluid elements of the organism 

18 



274 PRINCIPLES OF THERAPEUTICS 

and constitute a more highly developed medium (C. Fleig), 1 
is quite possible, even probable. As such, the isotonic marine 
serum may share in the same advantages; but let it not be 
presented to us as a regenerator of mediums, on the pretext of 
the marine origin of life! For that is merely an imaginary 
conception that can have no influence on a therapeutist who 
feels the need of scientific certainty. 

As long as there is no more than doctrinal affirmation, we 
may content ourselves with a skeptical smile; but when thera- 
peutics becomes crowded with such boisterous invaders, we 
must demand well-observed facts. The trouble is that when 
the facts are somewhat closely studied, we are disappointed. 
For example, I have before me an observation relative to the 
employment of marine serum in syphilis. It is said therein 
that the organism is repaired as if by enchantment; the lesions 
are cured with surprising rapidity, etc., etc., and it is only in 
the last lines that we are told that the patient was at the same 
time given specific medication! 

The first requirement of a therapeutic observation is to 
possess the value of a scientific fact. Therefore, it must 
include an accurate diagnosis of the disease and of the patient. 
It is indispensable for all the elements of this diagnosis (namely, 
all the findings upon which it rests) to possess, whether by 
themselves or by virtue of their groupings and their respect- 
ive chronology, the characters of certainty, as we have al- 
ready dwelt upon them. But it is also well to bear in mind 
that this diagnosis will be subjected to criticism and that, 
therefore, the latter must be furnished with the necessary 
elements of appreciation. It is not sufficient to say, as is 

1 C. Fleig, Academie des Sciences, July 1, 1907. 



METHOD IN THERAPEUTICS 275 

too often said, "the patient is tuberculous." It is neces- 
sary to say how long, on what precise signs the diagnosis 
rests, what are the exact characters of cough and expector- 
ation, the result of the bacteriological analysis, the course 
of the lesions, the temperature at rest and after exercise. 
Even this much is not sufficient; in the particular case it is 
necessary also to give information about the state of circu- 
lation, the pulse-rate, the blood-pressure, the size of the heart, 
the character of the heart sounds, the state of the digestional 
tract, the appetite, the functional activity of the stomach 
and the degree of facility with which this organ evacuates 
itself, the state of the liver and intestines, the analysis of the 
urine, not according to the antiquated fashion, but with the 
new data concerning the influence of alimentation on urine. 
If it is a woman, the regularity and quantity of menstru- 
ation, the pregnancies and lactation must also be included 
in the description. The probable development of the le- 
sions cannot be appreciated without these elements. It 
goes without saying that the data habitually contained in 
observations on the hereditary and personal antecedents 
(particularly adenopathy and previous pleurisy) must be 
noted. 

Even the best studied clinical observation may be inade- 
quate from a therapeutic point of view. In fact, it stops 
with the diagnosis and the progress of the illness. A clinico- 
therapeutic observation is necessarily far more complicated, 
because, besides the data of clinical observation, it includes 
the knowledge of the organs that are free from lesion, and 
of all the functions, an appreciation of the prognosis, and 
a record of the effects of the treatment. 



276 PRINCIPLES OF THERAPEUTICS 

The Importance of the Idea of Prognosis. — Besides these 
details, exposed as clearly as possible, it is indispensable to 
formulate the probable prognosis. This is one of the most 
difficult problems of medicine, so much so that, among the 
multitude of books that exist on all questions of medicine, 
there is none (so far as I am aware) devoted to prognosis. 
And yet, how is it possible to reach a conclusion as to the 
influence of a remedy if one has not previously formed an 
idea as to how the malady would have developed without 
the influence of the remedy? It is just here that one is 
obliged to admit the intervention of probabilities, which as- 
sume importance by virtue of their number, because it is 
obvious that by training oneself in this task of prognosis 
one will attain the ability to fulfil the task without often 
falling into error. The errors of prognosis must evidently 
be reckoned with in the calculation of probabilities, but the 
general result will be exact. 

At any rate, prognosis does not mean divination. It is 
by no means necessary to announce the issue of the malady: 
death or recovery at the end of a certain period of time. It 
is sufficient simply to say whether the progress of the disease 
appears to be regular, which carries the habitual prognosis 
of the morbid state, irrespective of any new complication 
impossible to forsee, or whether, on the contrary, the regular- 
ity of the development is threatened by the shortcoming of 
such and such an organ or by an existing complication, or by 
the general condition strictly defined. 

No matter what the disease may be, it is in all cases indis- 
pensable to proceed in this manner, basing the diagnosis on 
exact reasons and indicating the functional activity of all the 
organs. 



METHOD IN THERAPEUTICS 277 

Intervention of Treatment. — Finally, the action of the reme- 
dies that intervene must be studied. The influence they 
exert on the patient and on each of his organs, on the symp- 
toms each taken separately and on the malady in general, 
must accurately be described. One must not be contented, 
in the generality of cases, with establishing the curative power 
of a mode of treatment: the duration of the disease and of 
convalescence, the intensity of symptoms, complications, and 
disposition to relapse, may undergo important modifications 
to be reported. The organism has at its command so many 
resources that, in spite of reprehensible therapeutics, it may 
recover. However, there is a difference, I should say, between 
two patients who recover, one well taken care of and carried 
safely and without accident through the disease; the other 
with death hovering over him for several days. 

The influence of the therapeutic agent on the develop- 
ment of morbid phenomena is to be deduced from the phe- 
nomena observed and from the probable prognosis. One of 
the greatest difficulties in the appreciation of the effects of a 
remedy, and one of the most common causes of error lies in 
attributing observed effects to this or that therapeutic action 
taken by itself. Except in the case of specific treatment, 
prescription is very seldom, if ever, limited to a single thera- 
peutic action. Hygiene is almost always called into play 
concurrently with medicinal agents. How often are beneficial 
effects due to the former attributed to the latter? This error 
is more liable to occur in hospitals. A poor patient, depressed 
by poverty, inadequate nourishment and overwork, is taken 
in and given rest, suitable alimentation, and, at the same 
time, some medicine. Considerable improvement results in 



278 PRINCIPLES OF THERAPEUTICS 

the patient's state which is credited generally to the drug 
administered. The same drug is subsequently prescribed to 
a patient suffering from the same disease at his home, but 
it produces no notable results, because in this case there 
is no such revolution in hygienic conditions and environ- 
ment. 

Whenever it is desired to prove the action of a medicine, 
its action must be isolated, viz., it must be prescribed in the 
course of an organic stability as probable as it can be, as is 
often the case in tuberculosis, albuminuria, diabetes, car- 
diopathy, and neurasthenic states. Even then conviction 
cannot be final; for, notwithstanding all this precison, error 
is possible. A certain number of observations should pro- 
duce successively the same effects in order to warrant the 
conclusion that the particular mode of treatment is respon- 
sible for them. 

It is under these conditions of accuracy that a therapeutic 
observation acquires the value of a scientific fact. Ephem- 
eral enthusiasm will then less frequently be provoked by 
medicines and the public will be less skeptical in regard to 
physicians. 

This general line of conduct may be modified when, for 
instance, the curative action of a medicine on a certain dis- 
ease is to be determined. It is especially under such circum- 
stances that danger of post hoc, ergo propter hoc should be 
guarded against. The recovery of one patient would have 
little value. This is the reason that statistics are often re- 
sorted to, which sometimes pretend to replace by numbers 
the value of observations. 



METHOD IN THERAPEUTICS 279 



STATISTICS IN THERAPEUTICS 

What is the value of statistics in therapeutics? This ques- 
tion has been the object of numerous discussions. Statistics 
have had their advocates (Golfin, Louis, Chomel, Fonssa- 
grives), and adversaries (Risueno d' Amador, Trousseau, CI. 
Bernard), as well as their theorist (Gavarret). To-day sta- 
tistics are accepted; they render incontestable services; they 
are even indispensable to establish the comparative value of 
various therapeutic procedures; but statistical method does 
not constitute a real scientific method, since it could hardly, 
by itself, establish certainty, even empirical. Its value is 
mostly that of control and comparison, and even this it 
cannot do unless it obeys certain rules which are: 1. to be 
concerned with similar morbid states; 2. to consist of well 
observed units; 3. to bring together large numbers. 

It is evident that only units of the same kind can be added, 
but here the difficulty lies in the correct identification of 
cases. This should result from: 

1. Identity of the subjects of one group, from the view- 
points of age, sex, temperament, constitution, diatheses 
and environment. 

2. Identity of diseases. 

3. Identity of morbid forms. 

4. Identity of prognosis. 

5. Identity of therapeutic means and identity of purpose 
(cure, symptomatic or functional amelioration, or reparation). 

6. Identity of means of observation. 

Formerly statistics considered simply the influence of thera- 



280 PRINCIPLES OF THERAPEUTICS 

peutic procedures upon recovery or death. When limited 
to this consideration, therapeutics is very imperfect: statis- 
tics must further be concerned with the influence of thera- 
peutics on the duration of disease, gravity of symptoms, 
convalescence, facility of relapse, and amelioration of chronic 
conditions in general or particular functions. 

The value of a scientific method capable of engendering 
certainty should not be attributed to statistics even when 
they are otherwise irreproachable; they are defective in 
one thing: There can never be identity of cases composing 
them. Nor can one statistical table ever rigorously be 
compared with another, because it is impossible to agree 
on appreciations that have no criterion. Thus, in order 
to identify cases, authors often group them together as 
grave and benign; but what is a grave case? There are as 
many different answers as there are observations. So long 
as a typhoid fever remains regular, whatever its intensity, 
can it be called grave? And this other case, apparently most 
benign till the day when a perforation will cause a fatal termi- 
nation, how shall it be designated? As the appreciation of 
gravity of cases lacks accuracy, so the best statistics are 
devoid of the character of scientific precision. At a certain 
epoch the name diphtheria was refused to any case of pul- 
taceous sore throat that was not grave; now, in a large num- 
ber of instances, the diagnosis is deduced from the presence 
of Loeffler's bacillus in the exudate, without taking into account 
the degree of gravity. 

Well prepared statistics, namely, those composed of com- 
parable units, would be a highly valuable means of control 
and appreciation, which, as far as possible, should defini- 



METHOD IN THERAPEUTICS 281 

tively be substituted for vague impressions, so liable to deceive; 
but they can never, in general, be regarded as possessing abso- 
lute scientific precision. 

Summary 

In brief, therapeutics, like all sciences, must start with 
facts. Therapeutic facts are extremely complex and there- 
fore very difficult to establish. This circumstance renders 
it necessary to reduce them, by analysis, to their simplest 
elements, which can more easily be appreciated. To this 
end observation and experimentation are employed. 

The appreciation of the influence of a therapeutic measure 
is always derived from the idea that is formed of the diagnosis 
— an element which should be brought as near perfection 
as possible, in spite of the difficulties surrounding its study. 

In clinical observation the tendency to confuse facts, inter- 
pretations and opinions is to be guarded against. Facts 
alone have scientific value, provided they are demonstrated 
to be strictly certain. Numbers add less to the value of 
conclusions than does precision. 

Hypotheses and theories are not anti-scientific methods; 
but in therapeutics it is necessary to be reserved with these 
methods, because it is incorrect to apply to human beings 
conclusions that are still doubtful. 

Statistics are employed in therapeutics to establish the com- 
parative value of utilizable procedures. Good statistics 
imply several conditions, the most important of which is the 
identity of the elements composing them. They are vitiated 
by the difficulty of establishing this identity, and by differ- 
ences of individual appreciation. 



CHAPTER XII 
DIVISION OF THERAPEUTIC AGENTS 

Therapeutics does not admit of natural classification in 
the proper sense of the term: the multiplicity and diversity 
of its means as well as the too frequent uncertainty of their 
mode of action admit of artificial classifications above, or, 
rather, divisions; and even these are very difficult to establish. 
In fact, there are very few, if any, therapeutic agents with a 
simple action. Many possess several properties, and one is 
often embarrassed in placing them in this or that division 
while they could with just as good reason be grouped with 
another. 

One should not be fettered by these difficulties: therapeutics 
is not a simple science; it is a composite science that borrows 
its elements wherever it finds them. It utilizes morals as 
well as medicaments, the simplest water as well as the most 
complex chemical substance, the commonest hygiene as well 
as the most specific serum. It would be as useless as 
childish to seek to co-ordinate such dissimilar elements in nar- 
row divisions that would be incessantly overrun. It is neces- 
sary to take a larger view and be satisfied with grouping thera- 
peutic agents in accordance with the most practical principle, 
without much regard for the inevitable overlappings that 
would result from the manifold actions of these agents and 
the doubts that still persist as to the mode of action of a cer- 
tain number among them. 

282 



DIVISION OF THERAPEUTIC AGENTS 283 

This most practical principle seems to me to be the one I 
have established in regard to the four forms of therapeutic 
action: specific, functional, symptomatic, reparative. All the 
agents of therapeutic action can be placed in some one of 
these four categories. There will necessarily be found some 
medicines of yet uncertain action, like arsenic, which will be 
given a provisonal place in this division, but any other classi- 
fication would have the same drawback. With this reser- 
vation, I lay down the following division of therapeutic 
agents. 

Note. — In order not to make too long an enumeration, I shall 
cite only the principal representatives or agents of each group. 

FIRST CLASS 

Agents of the Therapeutics of Disease or Nosocratic 

Agents 

A. Medicines 

First group: Specific medicines. 

Quinin and its succedanea for malaria. 

Salicylate of soda and its derivatives, antipyrin, for 
acute articular rheumatism. 

Colchicum for gout. 

Mercury and its salts, iodics (iodid of potassium, lip- 
iodol, iodopin), atoxyl and arsacetin against syphilitic 
accidents. 

Iodics against sporotricosis. 

Second group: Indifferent anti-infectious medicines (non- 
specific or non-differentiated). 
Colloidal metals. 



284 



PRINCIPLES OF THERAPEUTICS 



NUCLEINATE OF SODA. 

Physiological salt water, so-called artificial serum 
(simple serum and complex serums). 
Revulsives. 
Abscesses, purposely produced. 

Third group: Antiseptics. 

I. Mineral antiseptics. 

1. Metals: Silver. 

2. Metalloids: Iodin, peroxid of hydrogen, chiorin. 

3. Acids: Boric acid, sulphurous acid. 

4. Bases: Lime, soaps. 

5. Metallic salts: Chlorid of zinc, permanganate of 
potassium, mercury salts. 

II. Organic antiseptics. 

1. Derivatives of methane: Formic acid, formal- 
dehyd, iodoform. 

2. Derivatives of propane: Lactic acid. 

3. Antiseptics of the aromatic series: Carbolic acid 
and its derivatives, resorcin, guaiacol, ichthyol(f), 
salicylic acid, benzoic acid, naphthols, microcidin. 

Fourth group: Antiparasitics. 

I. Parasiticides. 

1. Zoicides: Sulphur, petroleum. 

2. Mycicides: Tincture of iodin. 

II. Parasitifuges. 

1. Tenifuges: Grenadier root, pelletierin, kousso, male 
fern. 

2. Vermifuges: Semen contra and santonin. 



DIVISION OF THERAPEUTIC AGENTS 285 

Fifth group: Antidotes. 

I. Chemical neutralizers. 1 

1. Ant-acids: Alkalies. 

2. Ant-alkalies: Dilute acids. 

3. Chemical antidotes: 

Poisoning by arsenic: Peroxid of iron, protosulphate of 
iron, hydrate of magnesia. 

Poisoning by copper: Sugar, albumin. 

Poisoning by lead: Sulphur, dilute sulphuric acid, soluble 
sulphates. 

Poisoning by cyanics: Ferric hydrate^ 

Poisoning by mercurials: Milk, albumen. 

Poisoning by toxic alkaloids: Iodo-iodid of potassium, 
tannin. 

II. Eliminators of toxic substances, diuretics, su- 

DORIFICS, LAXATIVES, ETC. 

B. Biological Agents 
First group: Remedies derived from the organism of 
immunized animals: Specific serums. 

Second group: Remedies derived from bacterial products: 

Tuberculin (vaccines). 

Third group: Remedies derived from the organism of 
infected animals: Antirabic emulsion. 

C. Physical Agents 

First group: Phototherapy against lupus. 

Second group : Radiotherapy against epithelioma of skin, 
angioma, keloids, certain CHRONIC skin diseases. 

1 The group of antidotes is borrowed from the division of Fonssagrives; 
the disposition alone is changed. 



286 PRINCIPLES OF THERAPEUTICS 

Third group: Radiotherapy against pityriasis, sycosis, 
and epithelioma of the skin. 

D. Hygienic Agents, 
Eliminators. 

1. Water (hydric diet): mineral waters or amineral- 
ized waters (Evian, certain Vals, Pougues, etc.). 
Diuretic beverages, etc. 

2. METHODIC COLD BATHING. 

SECOND CLASS 

Agents op Organic and Functional Therapeutics 

A. Medicines 

First group: Modifiers of the organs of digestion and of 
their functions. 

I. 'Mouth and throat: Sialagogues. 
II. Stomach. 

1. Emetics: Ipecacuanha, tartar emetic, apomorphin. 

2. Excitants of the stomach: 

a. Pure bitters: Gentian, quassia, columba. 

b. Aromatic bitters: Humulus, chamomile. 

c. Astringent bitters: Cinchona, condurango. 

d. Aromatic essences, umbelliferous: Anisum. 
Labiates: Mentha, melissa, sage. 
Aromatic condiments: Cinnamon, saffron, 

3. Depressors of the gastric secretion: Sulphate of 
soda. 

4. Modifiers of the composition of the gastric juice: 
Hydrochloric acid, pepsin, gasterin, diastases. 



DIVISION OF THERAPEUTIC AGENTS 287 

5. Neutralizing substances : Bicarbonate of soda, pre- 
pared chalk, calcined magnesia. 

6. Evacuant substances: Bicarbonate of soda. 
III. Intestine. 

1. Purgatives. 

A. Simple evacuants: 

a. Saline purgatives: Sulphate of magne- 
sia, sulphate of soda, etc. 

b. Cathartics: Senna. 

c. Oils: Castor oil. 

d. Sugars: Manna. 

e. Mechanical purgatives : Grains of white 
mustard. 

B. Drastics: 

a. Chologogues: Aloes, podophyllin. 

b. Hy dragogues : Colocynth, gamboge. 

C. Calomel. 

2. Anticathartics : Subnitrate of bismuth. 

Second group: Modifiers of the heart and of circulation. 

1. Heart tonics: Digitalis, strophantus. 

2. Heart Stimulants: Spartein, caffein. 

3. Vaso-constrictors: Ergot, adrenalin. 

4. Vaso-dilators: Iodids. 

5. Hypotensors: Nitrate of amyl, trinitrin. 

Third group : Modifiers of the blood. 

1. Modifiers of the coagulability of the blood: 
Gelatin, chlorid of calcium. 

2. Depletive blood-letting. 



288 PRINCIPLES OF THERAPEUTICS 

Fourth group: Modifiers of bronchial secretions. 

I. Hypercrinics : Antimonials, ipecacuanha. 
II. Hypocrinics: Terpin, gomenol, eucalyptol. 

Fifth group: Modifiers of the functions of the nervous 
system. 

I. Excitants of the brain: Alcohol, coffee, tea. 
II. Excitant of reflex power: Strychnin, brucin, 
ammoniacals. 

III. Modifiers of reflex power: Bromids, belladonna 

and atropin, hyoscyamus. 

IV. Modifiers of the peripheral nervous system: 
Conium, aconite, eserin. 

V. Neuro-muscular modifiers: Veratrin. 

Sixth group: Modifiers of the sudoral function. 

I. Sudorifics: Jaborandi and pilocarpin, guaiacum, 
sarsaparilla, sassafras. 
II. Antisudorifics : Camphoric acid, tellurate of soda, 
sage, agaricinic acid. 

Seventh group: Modifiers of lacteal secretion. 

I. Galactogogues: Galega, anisum, fennel, nettle. 
II. Agalactics: Antipyrin, iodids, belladonna, cam- 
phor, purgatives. 

Eighth group : Modifiers of the urinary function. 

I. Diuretics. 

1. Cardio- vascular diuretics: Digitalis, caffein. 

2. Renal diuretics: 

a. Epithelial functional: Lactose, theobromine 
nitrate of potash. 



DIVISION OF THERAPEUTIC AGENTS 289 

b. Renal irritants: Gin berries, copaiba{1), can- 
iharidesC!) . 
II. Anurics: Purgatives, valerian, morphin, antipyrin, 
tannin. 

Ninth group: Modifiers of the genital apparatus. 

I. Emmenagogues: Apiol, groundsel, artemisia, sabina, 
rue. 
II. Aphrodisiacs: Yohimbin. 

Tenth group : Modifiers of nutrition. 

I. Accelerators of disassimilation: Chlorid of 
sodium, alkalies, temper ants (vegetable salts, organic acids). 
II. Diminishers of fat(?): Lithini^), piperazin, lycetol, 
urotropin, oxidants (vanadate of soda, etc.). 

Eleventh group (provisional) : Suppliers : all the products of 
opotherapy. 

Twelfth group (provisonal) : Protectors (?) : cholesterin(?), 
paratoxin(?). 

B. Hygienic Agents 
First group: Climate. 

I. Stimulating climates: 

1. Stimulation by obligatory adaptation: Altitude, 
cold countries, hot countries. 

2. Stimulation by the elements of climate: Dry 
climates. 

II. Sedative climates: Climate rendered little variable 
by the existence of natural shelters. 

Second group: Mineral waters. 

J9 



290 PRINCIPLES OF THERAPEUTICS 

Third group: Hydrotherapy. 
Fourth group: Antidyspeptic diet. 

C. Mechanical Agents 

CIRCULATORY AND NERVOUS MODIFIERS 

I. Massage (general and local). 

II. Position of the body and limbs. 

D. Physical Agents 

Modifiers of the nervous system, of the muscles, and of 
nutrition: Electricity, light, colors. 

THIRD CLASS 

Agents op Symptomatic Therapeutics 
A. Medicines 
First group: Modifiers of pain. 

I. General anesthetics: Ether, chloroform, chlorid 
of ethyl, nitrous oxid. 

II. Local anesthetics: Cocain, stovain. 

III. ANALGesics: Opium, morphin, solanacece, conium, 
aconite. 

Second group: Hypnotics. 

I. Direct hypnotics: Paraldehyd, sulphonal, trional, 

veronal, chloral. 
II. Indirect hypnotics: Opium and its derivatives, 
bromids. 

Third group : Antipyretics. 

Antipyrin, pyramidon, phenol, phenacetin, lactophenin, sali- 
cylic acid. 



DIVISION OF THERAPEUTIC AGENTS 291 

Fourth group : Antispasmodics. 

Valeriana, asafetida, castoreum, camphor, aqua laurocerasi. 

Fifth group: Cough sedatives. 

Opiates, solanacece, drosera, grindelia robusta. 

Sixth group: Eupneics. 

Heroin, pyridin, ammonia(1). 

Seventh group: Aperients. 

Persodin, vanadate of soda, orexin. 

B. Physical Agents 

Packing or tamponing of cavities (nasal cavity, vagina). 
Massage. 

FOURTH CLASS 

Agents of Reparative Therapeutics 
A. Medicines 
First group: General reparatives. 

Organic phosphates (phytin, lecithin), iron, mineral 

PHOSPHATES(?), PHOSPHORIC ACID, MEDICINAL FAT BODIES 

(cod-liver oil). 

Second group: Modifiers of disassimilation. 

Arsenic. 

Third group: Modifiers of the tissues. 
I. Caustics. 

1. Acids: Chromic acid. 

2. Alkalies: Lime, potash. 

3. Salines: Nitrate of silver. 
II. Astringents. 



292 PRINCIPLES OF THERAPEUTICS 

1. Vegetable: Tannin and its derivatives, gallic 
acid and its derivatives. 

2. Minerals: Alum, acetate of lead, chlorate of potash. 
III. Emollients. 

1. Mucilaginous: Gum arable, mucilages. 

2. Amylaceous and sugared substances: starch 

3. Gelatin. 

4. Fatty bodies. 

a. Oils. 

b. Fatty substances: Lard, cacao butter, lanolin, 
etc. 

c. Fatty substances of mineral origin: Vaselin. 

5. Antiseptic topica. 

6. Antiseptics to the organs. 

a. Antiseptics to the stomach: Peroxid of 
magnesium. 

b. Antiseptic to the intestines: Benzo-naphthol, 
salacetol. 

7. Modifiers of the urine: Copaiba, santal, uro- 
tropin, helmitol, salicylic acid and its derivatives. 

8. Delators: Laminaria. 

9. Uniters: Adhesive plaster, English taffetas. 

10. Adhesive preparations: Traumaticin, collodion. 

11. Absorbents: Absorbent powders. 

B. Hygienic Agents 

First group: Aliments and beverages. 

Milk, kefir, koumys, matzoon, or zoolak, meat powder, 
somatose, etc. 

Second group: Diet. 



DIVISION OF THERAPEUTIC AGENTS 293 

Milk diet, diets in various diseases. 

Third group: Conditions of Environment. 

Temperature, cleanliness, ventilation. 

Fourth group: Conditions of activity. 

Rest, exercise, gymnastics, neuromuscular reeducation. 

C. Mechanical Actions 
First group: Depurative blood-letting. 

Local blood-letting, derivatives. 

Second group: Orthopedics. 

Third group: Mechanotherapy. 

Fourth group: Reductions. (Dislocations, Jiernia). Main- 
taining of an organ in place, compression, dilatation, Bier's 
method. 

Fifth group: Washing of the organs. (Bladder, stomach). 

Sixth group : Tapping of the Organs. (The pleura, the peri- 
cardium, the peritoneal cavity, the bladder, cysts). 

D. Psychic Actions 

Suggestion in the Hypnotic State, Suggestion During 

the Wakeful State. 

Psychic education and reeducation. 

E. Physical Agents 

Heat: Cauteries (thermo- and galvano-cauteries). 
Sparks of high frequency (fulguration). 

F. Surgical Actions 

Incision, excision, exclusion, amputation, scraping, curettage. 



INDEX 



Absorption of medicines, conditions 
favorable to, 159; by skin, 222; 
by wounds and mucous mem- 
branes, 223. 

Administration of medicines, 157. 

Age, an element of therapeutic 
individualization, 134. 

Aged, cautions in treatment of, 138. 

Alternation of medicines, 109. 

Anomalies, conduct of physician in 
presence of, 91. 

Antidotes, 32, 285. 

Antipyretics, contraindication of, 
during menstruation, 133; in chil- 
dren, 136. 

Apathy to medicines, 160. 

Asepsisof medical preparations, 216. 

Assuetude, 171. 

Attendants, 24. 

Bathing, cold, 233. 
Body-fluids, resisting and defensive 
power of, 38. 

Capsules, 212. 

Capsulins, 212. 

Chemical structure of medicines, 199. 

Children, particular posology for, 
134; special susceptibilities of, for 
certain medicaments, 136; high 
temperature in, 136. 

Climate, therapeutic role of, 179; 
change of, 230; division of, 289. 

Clinical observation from therapeu- 
tic standpoint, 271. 



Color, therapeutic influence of, 179. 
Constitution, as an element of 
therapeutic individualization, 143. 
Consultations, 186. 
Crayons, 213. 

Decay, as an element of therapeutic 
individualization, 144. 

Diathesis, definition of, 144; as an 
element of therapeutic individ- 
ualization, 143. 

Dietetics, 229, 293. 

Diffusibility of medicines, 195. 

Digitalis, difficulties in employment 
of, 98, 122. 

Disease, definition of, 58 ; constituent 
elements of, 57; an element of 
therapeutic individualization, 154; 
new manner of being created by, 
148, 150. 

Diuretics, 288. 

Doses, 76, 91, 105; massive, 223; 
too large, 76; large, 80, 83; the 
smallest efficacious, 78, 107; tables 
of maximum, 124; division of, 
126; for the aged, 138; fractional, 
224; functional, 81; reparative, 
86; specific, 81; symptomatic, 85; 
seven rules for management of, 
105. 

Dragees, 211. 

Durst's procedure, 135. 

Electricity, 250. 

Electrolytic dissociations, 196. 



295 



296 



INDEX 



Embryocardia, 98. 

Emetics, 286. 

Emmenagogues, 289. 

Empiricism, 16, 48. 

Enemata, 221. 

Entourage, therapeutic influence of, 
182. 

Environment, influence of, on thera- 
peutic results, 176; influence and 
utilization of, in favor of the sick, 
228. 

Erethism, medicinal, 174. 

Etiocratic therapeutics, 26. 

Etiological therapeutics, 26. 

Expectation, 48. 

Experimentation (in therapeutics), 
265. 

Formulae, 125. 
Formularies, 122. 
Functional therapeutics, 127, 153. 
Furniture, therapeutic influence of, 
181. 

Galactogogues, 288. 
Gelules, 212.* 
Globules, 212. 
Granules, 211. 

Habituation or assuetude, 171. 
Harm (in therapeutics), 114; eight 

rules for avoidance from doing, 

127; can be done by defect, 114; 

by excess, 115; by insufficiency, 

118; by negligence, 120. 
Health and disease, 56. 
Hydrotherapy, 233. 
Hygiene, therapeutic, 226. 
Hygienic actions, 226. 
Hygienic agents, 286. 
Hypnotism, 241. 
Hypothesis, value of, in therapeutic 

research, 262. 

Idiosyncrasy, 169. 



Inactivity of medicines, 163. 

Individuality (of patient), elements 
constituting, 130. 

Individualization, therapeutic, 130. 

Injections, 158; subcutaneous, intra- 
muscular, intravenous, 158, 218; 
intratracheal, spinal, and intra- 
visceral, 223. 

Ionic dissociations, 196. 

Intolerance (to medicines), 164. 

Iron, not a mere restorative, 105. 

Isolation, psychic action of, on 
patient, 244. 

Keratinization, 211. 

Lactation, therapeutic intervention 

during, 134. 
Light, therapeutic influence of, 179. 

Mechanical action (in therapeutics), 
246. 

Medicaments or medicines, defini- 
tion of, 23; doses of, 76; alterna- 
tion of, 109; anti-infectious, 30, 
283; antiparasitic, 32, 284; anti- 
septic, 31, 284; toxic action of, 55; 
physiological action of, 63; utili- 
zable action of, 66; therapeutic 
action of, 66; variation of action 
of, in different diseases, 154; 
influence of route of introduction 
of, on their activity, 217; different 
modes of reaction of patients to, 
155; activity of, in proportion to 
solubility, 194; relation between 
physiological and curative effects 
of, 105; use of corrective, 126; 
nosopoietic, 50; specific, 28, 283; 
chemical structure of, 199. 

Medicinal opportunity, 88. 

Medicine, the teaching of , 111, 121. 

Menstrual period, use of medica- 
ments during, 138. 



INDEX 



297 



Mercury in infantile therapeutics, 

137. 
Mucous membranes, absorption of 

medicines by, 223. 
Musicotherapy, 250. 

Nosocratic medicines, 27, 152. 
Nurses, importance of role of, 182. 
Nutrition, modifiers of, 289. 

Observation (in therapeutics), 265. 
Oligopharmacy, 112. 
Opotherapy, 5, 37. 
Ovules, 212. 

Paraspecific value of medicines, 52. 

Pastes, 212. 

Pastilles, 212. 

Patient, knowledge of, 25; organs 
and functions of, as elements of 
therapeutic individualization, 148, 
155; preparation of, to action of 
medicaments, 153. 

Perls, 212. 

Persuasion (in psychotherapy), 242. 

Pharmacist, 191. 

Pharmaceutic forms, influence of, 
on activity of medicines, 207. 

Pharmacodynamics, 24. 

Pharmacology, 23. 

Pharmacotherapy, 24. 

Pharmacotoxinic synergy and antag- 
onism, 69. 

Physical action (in therapeutics), 
248. 

Physical agents, 285. 

Physician, hard beginning of career 
of, 88; guiding principles for, 89; 
therapeutic influence of person- 
ality of, 111; good, 130; therapeu- 
tic role of, 184; consultant, 187; 
change of physician, 189. 

Physiotherapy, 5, 225. 

Pills, 210. 

Pneumotherapy, 250. 



Poisons, 31; prescription of doses of, 
126. 

Polypharmacy, 112. 

Posology, need of revision of, 124. 

Powders, 210. 

Pregnancy, therapeutic interven- 
tion during, 133. 

Prescription, 24; duration of a, 107; 
for poor patients, 117; execution 
of, 124, 129; formularies and, 122. 

Prognosis, importance of idea of, 276. 

Psychic actions, 234. 

Psychotherapy, 234; by reasoning or 
re-education, 242. 

Pulse in typhoid fever, 95. 

Quinin, 132. 

Radiotherapy, 249. 

Radiumtherapy, 249. 

Reaction of organism to thera- 
peutic doses of medicines, 159. 

Reasoning, value of, in therapeutic 
research, 260. 

Recovery, spontaneous, 153. 

Rectum, route of introduction of 
medicines, 159. 

Re-education of mind, 242. 

Religious faith, important psychic 
action of, on patient, 244. 

Remedy, definition of, 23; knowl- 
edge of, 25. 

Rest, 233. 

Revulsion, 51. 

Season, therapeutic influence of, 179. 

Serumtherapy, 5. 

Sex, as an element in therapeutic 

individualization, 131. 
Skin, absorption of medicines by, 

222. 
Solubility of medicines, 194. 
Solutions, 210. 
Specialties, 213. 
Statistics in therapeutics, 279. 



298 



INDEX 



Suggestibility, 238. 
Suggestion, 235; charlatanic, 234. 
Suppositories, 212. 
Symptoms, medication of, 100. 

Tablets, 212. 

Temperament, 139. 

Temperature, modification of medi- 
cinal action by, 150; therapeutic 
influence of, as an element of 
environment, 176; importance of, 
in medicinal drinks, 195. 

Theory, value of, in therapeutic 
researches, 261. 

Therapeutic activity, variation of, 
inherent in medicines, 193; in- 
herent in mode of administration, 
194. 

Therapeutic agents, division of, 282. 

Therapeutic facts, complexity of, 
255. 

Therapeutics, evolution of history 
of, 2 ; skepticism in, 3 ; scientific, 7 ; 
educative instruction in, 9; a 
composite and complex science, 
14; an art, 14; definition of, 15; 
empiricism in, 16, 19; variations 
of, 21; of disease, 26; etiocratic, 
26; etiological, 26; organic and 



functional, 34, 127, 153; delicate 
management of functional, 108; 
symptomatic, 39, 100, 128; speci- 
fic, 28; reparative, 42, 104, 129, 
291; non-medicinal, 226; method 
in, 251. 

Tolerance (to medicines), 160; path- 
ological conditions favorable to, 
162. 

Toxic action (of medicaments), 
definition of, 62. 

Toxicity, addition of medicinal, to 
morbid, 74. 

Treatment, intervention of, 277; 
number of specific, limited, 30. 

Typhoid, pulse in, 95; cold bathing 
in, 97. 

Ventilation, 181. 

Wafers, 211. 

Water, major remedial importance 
of, 229; mineral, 232. 

Women, excellent patients for thera- 
peutics, 131. 

Wounds, absorption of medicinal 
substances by, 223. 

Young's procedure, 135. 



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